IL-6 Values Research Articles

Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 μg/mL; LC50 26.73 ± 1.2 μg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

The Value of Prolactin, a Panel of Cytokines, and the Soluble Human Epidermal Growth Factor Receptor 2 in the Prediction of Rapid Progression and Shorter Survival during Palliative Chemotherapy of Colorectal Cancer Patients.

The prediction of colorectal cancer (CRC) response to palliative chemotherapy (CTH) is still difficult. Patients at a higher risk of progression may benefit from more aggressive treatment. This study assessed the predictive value of prolactin (PRL) and a panel of cytokines, chemokines, and growth factors for the risk of rapid progression in CRC patients starting palliative CTH. This study included 51 CRC patients initiating palliative CTH with up to 5-year follow-up, divided into rapid and non-rapid progressors. Serum samples were collected before CTH for assessment of a large panel of cytokines, chemokines, growth factors, and PRL via a multiplex method. Rapid progressors (N = 19) were characterized by increased baseline values of IL-8 and IP10 but decreased PRL levels. In addition, PRL below 18.2 ng/mL was a strong predictor of weight loss during CTH. Grade 3 (HR = 2.97; 95%CI: 1.48-5.98) and PRL level (HR = 0.96; 95%CI: 0.91-1.01) were independent risk factors of progression. We showed that CRC rapid progressors are characterized by decreased baseline PRL levels. In addition, increased baseline levels of IP-10, sHER-2, IL-6, and IL-8 may be associated with longer survival; however, larger studies are needed to confirm their predictive role in CRC patients.

Cytokine profile characterization of naïve patients with psoriasis and psoriatic arthritis: implications for a pathogenic disease continuum.

The idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients. By multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30). In 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others. Our findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients.

The relationship between neuropathic pain and serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, VEGF-A levels in fibromyalgia patients and molecular docking results

Purpose: The most important clinical finding of fibromyalgia syndrome (FMS) is pain. Its etiology has not been fully elucidated. This study was planned to determine the relationship between endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-a, VEGF-A levels and pain/neuropathic pain in FMS patients.
 Materials and Methods: Forty-four FMS patients who met the inclusion criteria and 44 age-matched premenopausal healthy controls were recruited. The fibromyalgia group was evaluated in terms of Visual Analog Scale, Beck Depression Scale, Beck Anxiety Scale, Fibromyalgia Impact Questionnaire and LANSS Pain Scale. Serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, and VEGF-A values were determined by the ELISA method. Protein-protein interaction was evaluated by molecular docking analysis. Bioinformatics analysis was performed using the STRING v 11.5 protein interaction tool.
 Results: Endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, and VEGF-A were significantly higher in FMS patients than the control group. 24 of 44 patients had neuropathic pain. No correlation was found between pain/neuropathic pain and serum markers levels. High interaction and homology scores of the proteins were defined.
 Conclusion: The pain/neuropathic pain relationship of these markers could not be determined, but the calculated binding energies and activities of the proteins provided important clues for future studies.

Predictive values of salivary IL-6 and sFas-dependent apoptosis inhibitor in pathogenesis of oral lichen planus

Predictive values of salivary IL-6 and sFas-dependent apoptosis inhibitor in pathogenesis of oral lichen planus

Additional value of interleukin-6 level to predict histopathological features of hepatocellular carcinoma before liver transplantation

Background & AimsInflammatory biomarkers are increasingly used as outcome predictors in the field of oncology and liver transplantation for HCC, but no study has shown the prognostic value of IL6 after LT.The goal of this study was to evaluate the predictive value of IL-6 on histopathological features of HCC on explant, its predictive value on recurrence risk and its additional value to other scores and inflammatory markers at the time of transplantation. MethodsFrom 2009 to 2019, all adults transplanted with a first liver graft and diagnosed with HCC on the explant analysis were retrospectively included (n = 229). Only patients who had a pre-LT IL6 level determination were analysed in this study (n = 204). ResultsHigh IL-6 level at transplantation was associated with a significantly higher risk of vascular invasion (15% vs 6%; p = 0.023), microsatellitosis (11% vs 3%; p = 0.013), lower rate of histological response both in terms of complete response (2% vs 14%, p = 0.004) and of necrosis (p = 0.010).Patients with pre-LT IL-6 level > 15 ng/ml had a lower overall and cancer-specific survival (p = 0.013).Recurrence-free survival was lower in patients with IL-6 > 15 ng/ml with a 3-year recurrence-free survival of 88% versus 78% (p = 0.034). IL6 levels were significantly higher in patients with early recurrence compared to patients without (p = 0.002) or with late recurrence (p = 0.044). ConclusionsIL6 level at transplantation is an independent predictor of pejorative histological features of HCC and is associated to the risk of recurrence.

1492-P: IL-8/CXCL8 May Identify a New Type 1 Diabetes Endotype

Recent research focused on identifying mechanisms explaining the observed heterogeneity of type 1 diabetes (T1D) in age at onset, residual β-cell function and rate of disease progression. Mechanisms include changes in both the immune system and β-cells, leading to the loss of tissue-specific immune tolerance and disease onset. Interleukin-8 (IL-8; CXCL8) is a pro-inflammatory chemokine released by macrophages, endothelial, epithelial and airway smooth muscle cells playing a major role in the innate immune response. Macrophages release IL-8 at the site of an injury where they recruit and activate neutrophils by interacting with the IL-8 receptors CXCR1 and CXCR2. An increase in circulating IL-8 has been shown in several autoimmune disorders. IL-8 levels, but not IL-6 or TNF-α, are elevated in adolescents with T1D, and also associated with insulin resistance, suggesting a role for IL-8 beyond acute inflammation in this setting. In vitro experiments revealed that IL-8 transcription is induced by hyperglycaemia. In the present study newly diagnosed T1D patients within the first year of disease onset (mean age 16.2 ± 7.6 yrs and % HbA1c of 10.7 ± 2.7) (N=42) were studied. Clinical and laboratory features included age, gender, body mass index (BMI), disease duration, HbA1c, and C-peptide. Serum IL-8 and myeloperoxidase (MPO) were measured with commercial enzyme-linked Immunosorbent assays. When compared to normal subjects, T1D patients showed a significantly higher IL-8 values (median [IQR] 112.0 [64.74-311.8] vs 43.05 [30.94-49.70], p-value= 0.002, respectively). Furthermore, T1D patients showed a significantly higher MPO levels than controls (median [IQR], 95327 [55718 - 168974] vs 42729 [24147 - 95327], p-value= 0.0349, respectively). This study shows for the first time that IL-8 and MPO are elevated in patients with recent onset T1D compared to normal subjects. There is also a trend for a positive correlation between IL-8 and HbA1c levels suggesting that elevated IL-8 values are associated with poor metabolic control. Disclosure G.Alhamar: None. S.Fallucca: Consultant; Dompé. S.Pieralice: None. L.Valente: None. P.Pozzilli: None.

#5536 CIRCULATING LEVELS OF COPEPTIN, GROWTH DIFFERENTIATION FACTOR 15 (GDF15) AND INTERLEUKIN 6 (ILA-6) IN PATIENTS WITH ADVANCED KIDNEY DISEASE

Abstract Background and Aims The search for new serum biomarkers of cardiovascular risk and mortality in patients with CKD is relevant to improve the monitoring of these patients. Copeptin is a glycopeptide that is released equimolarly with arginine-vasopressin. GDF-15 is a cytokine involved in macrophage activation processes and is a marker of response to oxidative stress, and IL-6 as a marker of systemic inflammation. Objective: To study the serum levels of copeptin, GDF-15 and IL-6 in patients with advanced CKD. Method Cross-sectional study in 32 patients with advanced CKD. In all patients, the estimated glomerular filtration rate (eGFR) was determined by CKD-EPI, the albumin/creatinine ratio (CrAI) and the serum concentrations of copeptin (immunofluorescence, Thermo Fisher), GDF-15 (chemiluminescence, Roche Diagnostics International) and IL-6 (Siemens Healthineers). Results were compared to laboratory reference values (RVs) for copeptin (VN<4.2 pmol/L) and IL-6 (VN<4.4 pg/mL). The VR of GDF-15 (708±227 pg/ml) corresponds to own data from 10 Blood Bank donors. Results for copeptin and GDF-15 (normal distribution) are shown as mean ± SD. IL-6 results (without normal distribution) as median and interquartile range. Results In CKD we observed an increase in copeptin (26.9±22 pmol/l, 90% >4.2 VR) and GDF-15 (4703±2683 pg/ml p<0.0001 vs. control population). Median IL6 3.2 pg/ml (IQR: 2.7-5.1, 35% >4.4 VR). We did not find differences in the levels of copeptin, GDF-15 or IL-6 based on age, sex and presence or absence of diabetes. A significant correlation was found between GDF15 levels and eGFR (r=-0.54 p<0.002). Conclusion Serum levels of copeptin and GDF-15, but not IL6, are increased in CKD patients. Our data suggest a significant inverse relationship between GDF15 and eGFR. More studies are needed to know the possible role of GDF-15 on the progression of kidney damage and cardiovascular complications in patients with CKD.

#3564 DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF INTERLEUKIN-6 IN LUPUS NEPHRITIS

Abstract Background and Aims Lupus nephritis is a frequent and potentially serious complication of SLE. The present study is aimed to evaluate the usefulness of urinary IL-6 as a non-invasive diagnostic & prognostic biomarkers of disease activity in LN. Method The study was done in IMS and Sum hospital, Bhubaneswar, India from January, 2018 to July 2022. The study included 20 healthy controls and 32 patients of SLE diagnosed based of Systemic Lupus International Collaborating Clinic (SLICC) criteria, who presented with renal involvement. The exclusion criteria was inability to obtain informed consent and SLE patients without renal involvement. Urinary IL-6 levels were assessed in patients before initiation of therapy and in controls by quantitative sandwich EASIA technique using human IL-6 EASIA kit (DIA Source Belgium). All patients underwent ultrasound guided renal biopsy and the results were classified according to the ISN/RPS classification of LN. Treatment was started in all patients according to class of LN as per KDIGO guidelines. Urinary IL-6 levels were again assessed in all patients after 6 months of induction phase treatment. Results In our 32 patients, female to male ratio was 7:1 with a mean age of 28.68 ± 9.28 years. In our study, ANA was positive in 96.8%, anti-dsDNA Ab in 78%, C3 was low in 78% & C4 was low in 72% of LN patients. Based on renal biopsy findings, there were 2 cases of Class II LN, 6 cases of Class III LN, 19 cases of Class IV LN and 5 cases of Class V LN. In our study, patients with LN have significantly higher urinary IL-6 levels (301.58 ± 483.96 pg/ml) as compared to 20 healthy controls (4.7±2.282 pg/ml) with a p-value = 0.001. The mean urinary IL-6 levels in different ISN/RPS classes of LN patients based on renal biopsy showed a statistically significant difference between different classes (p-value = 0.005). Highest values of urinary IL-6 (475.126 ± 580.90 pg/ml) was seen in Class-IV LN which is most active form of LN and lowest values (28.28 ±7.30pg/ml) were seen in Class-II LN. In our study, a significant correlation was found between serum creatinine & presence of active urinary sediment with urinary IL-6 levels but there was no correlation between 24 hour urinary protein with urinary IL-6 levels in patients of LN (p value = 0.799). In our study 2 patients (6.25%) died, 3 patients (9.37%) lost follow up, 16 patients (50%) achieved complete remission, 8 patients (25%) achieved partial remission and 3 patients (9.37%) did not show any improvement after 6 months treatment. Urinary IL-6 levels were near normal among 12 patients (75%) out of 16 patients who achieved remission after 6 months of induction treatment (p-value = 0.001). Urinary IL-6 levels remained elevated in all 8 patients (100%) who achieved partial remission (p-value = 0.028, and also remained elevated in all 3 patients who had no remission at all (p-value = 0.109). Conclusion Urinary IL-6 may provide a simple non-invasive potential biomarker of disease activity of renal involvement in patients with SLE and may be used to monitor therapy.

#4479 KIM-1, IL-18 AND NGAL IN MACHINE LEARNING PREDICTION OF KIDNEY INJURY AMONG CHILDREN UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract Background and Aims Children undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) are particularly vulnerable to acute kidney injury (AKI), especially in the early post-transplantation period. The major risk factors of AKI development are aggressive immunosuppression and infectious complications. In the meantime, malnutrition and hypermetabolic state of the patient, together with the routine intensive hydration during first 3 weeks after HSCT and subsequent forced diuresis, alter the serum creatinine concentration, modifying the estimated glomerular filtration rate (eGFR) value too. Therefore, the risk of underrating serum creatinine and overrating eGFR values is high, making the assessment of the degree of kidney damage during the first month after HSCT a challenge. Therefore, markers of tubular dysfunction and damage, like kidney injury molecule (KIM)-1, neutrophil gelatinase-associated lipocalin (NGAL) or interleukin (IL)-18, may be of added value while assessing renal function and analyzing the risk of AKI in this population. The aim of study was to assess the serum concentrations of damage biomarkers (KIM-1, NGAL, IL-18) in children undergoing alloHSCT, in relation to another surrogate marker of renal dysfunction, hyperfiltration. Another aim was to analyze the potential value of KIM-1, NGAL, and IL-18 as predictors of kidney damage in children after alloHSCT, with the use of artificial intelligence tools. Method The study group contained 22 children undergoing alloHSCT, followed up for 4 weeks after transplantation. Serum concentrations of KIM-1, NGAL, and IL-18 were assessed by ELISA in fixed time points (before HSCT, 1 day after HSCT, 1, 2 3, 4 weeks after transplantation). eGFR values (counted based on Schwartz formula) and the rate of hyperfiltration (eGFR > 140ml/min/1.73sq.m.) were evaluated at the beginning (before HSCT) and at the end (4 weeks after HSCT) of observation, when neither hydration nor diuretics were used. Statistical analysis was performed with the use of package Statistica, the comparisons between paired data were evaluated by using nonparametric tests (Friedman, Wilcoxon). Additionally, the patients within the database were randomly divided into two groups. The training group allowed to build a Random Forest Classifier (RFC) with the highest possible predictive power, while the testing group allowed to assess the effectiveness of prediction on new data and the clinical utility. Moreover, the contribution of individual variables was evaluated by GINI importance. Results KIM-1, NGAL, and IL-18 serum concentrations increased systematically until the 3rd week after HSCT, with statistically significant differences between subsequent observation points, then remained elevated until the 4th week after HSCT. Median eGFR values before transplantation and 4 weeks after HSCT were comparable, although the rate of patients with hyperfiltration increased. The RFC model built on the basis of 3 input variables, KIM-1, NGAL, and IL-18 concentrations in serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration 4 weeks after the procedure. RF Classifier achieved AUROC of 0.8333, accuracy of 80.00%, positive predictive value of 0.8667, and sensitivity of 0.8000. The contribution of KIM-1, IL-18 and NGAL to the prediction in this model was comparable (33.73%, 32.77%, and 33.5%, respectively). Conclusion KIM-1, NGAL, and IL-18 are useful in assessing acute tubular damage in children after HSCT. Their values before HSCT may also serve as markers of incipient renal dysfunction 4 weeks after alloHSCT. The developed model seems a clinically useful tool to target patients who are at risk of kidney injury after HSCT. The Random Forest Classifier seems a promising tool for such analysis, that should be tested on a larger group of patients.

#4229 SECONDARY BACTERIAL AND FUNGAL INFECTIONS IN COVID-19 PATIENTS WITH ACUTE KIDNEY INJURY AND RELATION WITH CYTOKINE STORM SYNDROME

Abstract Background and Aims Both COVID-19 and acute kidney injury (AKI) are associated with impaired host immunity. Virus-induced immunosuppression, overuse of antibiotics and corticosteroids are COVID-19 related factors, while dysregulation of the inflammatory response, increased volemia, hemodialysis catheters are AKI-related factors which favor secondary infections. We aimed to search the relation between markers of cytokine storm syndrome (interleukin-6 – IL-6; ferritin; C-reactive protein – CRP) and incidence of secondary infections and to identify the microorganisms involved in secondary infections in patients admitted with acute kidney injury and COVID-19 patients. Method Patients with both COVID-19 and AKI admitted in the 2nd and 3rd waves of the COVID-19 pandemic (May-December 2021) in an COVID-only hospital were included in this retrospective analysis. Diagnosis of AKI was established according to KDIGO creatinine-based criteria. Obstructive AKI cases were excluded. AKI was classified as A-AKI when it was diagnosed at the moment of admission and HA-AKI when it developed during hospitalization. Bacterial and/or fungal infections and the sites of positive cultures were registered in all patients. Colonizations with nonpathogenic microorganisms were excluded. Median values of IL-6, ferritin and CRP (maxim levels recorded during hospitalization) were compared between infected and non-infected patients. Results A total of 247 patients with AKI+COVID-19 were included in the study: 146 had A-AKI and 101 had HA-AKI. Secondary bacterial and fungal infections were registered in 111 patients (44.93%) cumulating 161 positive urine, blood, hemodialysis catheter tip, sputum, wounds, feces and tracheal intubation tubes cultures. Secondary infections were noted significantly more frequent in HA-AKI cases than in A-AKI cases: 61.38% (62 patients) vs 33.56% (49 patients) – Fischer exact test, p<0.001. The responsible microorganisms and the sites of positive culture are presented in Table 1. Median values of IL-6, ferritin and CRP (maximum levels recorded during hospitalization) were significantly higher in infected patients than in non-infected patients (Table 2) in the entire study group. IL-6 was significantly higher in infected HA-AKI patients when compared with infected A-AKI (231.40 pg/mL vs 124 pg/mL; p = 0.015), but no significant difference was found between the two subgroups of infected AKI patients regarding median ferritin levels (2481.5 ng/mL vs 1785 ng/mL; p = 0.324) or regarding median CRP values (206.27 mg/L vs 179.59 mg/L; p = 0.546). Conclusion Incidence of secondary bacterial and/or fungal infections in patients admitted with AKI and COVID-19 was very high in our study and it was associated with more severe altered markers of cytokine storm syndrome. Secondary infections in COVID-19 patients are important drivers of hospital-acquired AKI or they can aggravate its evolution.

#5951 INFLUENCE OF DIETARY INTAKE ON GASTROINTESTINAL SYMPTOMS AND INFLAMMATION MARKERS IN PERITONEAL DIALYSIS PATIENTS IN SLOVENIA

Abstract Background and Aims Gastrointestinal symptoms are prevalent in patients with end-stage renal disease. Gastrointestinal symptoms in such patients are related to gastric hypomotility, increased medication intake, uremia, and changes in diet. In addition GI symptoms and problems associated with bowel dysfunction are a common cause of technique failure and poor dialysis efficacy. The reason for presence of some gastrointestinal symptoms is also chronic inflammatory state. Inflammation can have many negative effects, including decreased appetite, accelerated protein skeletal muscle breakdown and hypercatabolism. Method 14 peritoneal dialysis patients were included in single Department of Nephrology in the University Medical Center in Ljubljana. All patients were interviewed by a dietitian and nutritional assessment was conducted. Gastrointestinal symptom Rating Scale (GSRS) with 7-grade Likert scale was used to evaluate the intensity of GI symptoms and Bristol Stool Form Scale (BSFS) to classify patient's stool. The dietary intake of peritoneal dialysis patients was assessed using 7-day food diaries and analyzed with Prodi program (PRODI® 6.4 Expert program, Stuttgart, Deutschland). Body composition has been measured with bio impedance spectroscopy. Routine blood analysis was performed. Results Among 14 patients undergoing peritoneal dialysis, most of them were male (71.4%) with average age of 53.07 ± 12.32 years. Average energy intake of 14 patients was 21.05 ± 5.72 kcal/kg body weight per day, average protein intake was 0.87 ± 0.39 g/ kg body weight per day and average fiber intake was 13.75 ± 7.25 g per day. They were inadequate according to the dietary guidelines for peritoneal dialysis patients. Average dietary protein-fiber index was 6.86 ± 3.81 per day. Average PRAL value was 15.84 ± 13.44 for women and 6.52 ± 17.99 for men. Average dietary potassium intake was 1917.80 ± 790.08 mg per day which corresponds to the guidelines for peritoneal dialysis patients and average potassium serum value 4.45 ± 0.42 mmol/L. GSRS questionnaire showed peritoneal patients had minor to mild discomfort in abdominal pain, constipation and indigestion GI symptom cluster. Patients’ self-analysis of stool showed BSFS Types 3.23 ± 1.64 if BSFS Types 3–5 are defined as normal stools. Dietary protein intake strongly correlated with dietary energy intake (r = 0.76, p = 0.003), dietary protein-fiber index strongly correlated with PRAL value (r = 0.70, p = 0.007) and dietary potassium intake moderately to strongly correlated with dietary fiber intake (r = 0.62, p = 0.025). Serum value of IL-6 strongly correlated with dietary potassium intake (r = 0.72, p = 0.006) and moderately to strongly correlated with dietary fiber intake (r = 0.6, p = 0.034). The correlation between dietary potassium intake and serum hsCRP was significant (p = 0.042). The correlation between Bristol stool consistency value and serum hsCRP was significant (p = 0.0255). The correlation between total GSRS score and serum value of albumin was significant (p = 0.0010). The correlation between total GSRS score and dietary potassium intake was significant (p = 0.0015). The correlation between total GSRS score and dietary protein-fiber index was significant (p = 0.0403). Conclusion Gastrointestinal diseases in peritoneal dialysis patients are comparatively understudied in the literature, despite having a significant impact on dialysis efficacy and the quality of life. Analysis of GSRS questionnaire showed that abdominal pain, constipation and indigestion caused minor to mild discomfort in PD patients. The analysis also showed that fiber intake, potassium intake and gastrointestinal symptoms are significantly associated with inflammation markers and are important contributing factors to chronic inflammatory state in these patients. Patients still lack the basic knowledge of nutrition, thus in the future nutritional consultations, innovative teaching techniques and help will be crucial to prevent the decline in nutritional status.

Comparison of Interleukin-6 with Other Markers in Diagnosis of Ovarian Cancer.

The lack of specific symptoms in ovarian cancer delays onset of the diagnostic process. Hence, most cases are recognized in late stages of the disease. The aim of this study was to confirm the role of Il-6 compared to other markers in diagnosis and survival in ovarian cancer. The database was collected from 13 January 2021 to 15 February 2023. In total, 101 patients with pelvic tumors with a mean age of 57.86 ± 16.39 participated in the study. In every case, CA125, HE4, CEA, CA19-9, Il-6, C-reactive protein and procalcitonin measurements were taken. Patients with ovarian borderline tumor and metastatic ovarian tumors were excluded from further analysis. Statistically significant correlations were found between diagnosis of ovarian cancer and levels of CA125, HE4, CRP, PCT and Il-6. Comparison of Il-6 with other markers revealed that longer overall survival correlated with lower values of Il-6. In the case of a higher concentration of Il-6, OS and PFS were shorter. Sensitivity and specificity of Il-6 in diagnosis of ovarian cancer were 46.8% and 77.8%, respectively, while for CA125, CRP and PCT were 76.6% and 63%; 68% and 57.5%; 36% and 77%, respectively. More investigations are needed to identify the most specific and sensitive marker for ovarian cancer.

Effect of a Physical Exercise Program on the Inflammatory Response, Cardiac Functions, Functional Capacity, and Quality of Life in Patients with Sickle Cell Disease.

The beneficial effects of physical exercise on functional capacity and inflammatory response are well-known in cardiovascular diseases; however, studies on sickle cell disease (SCD) are limited. It was hypothesized that physical exercise may exert a favorable effect on the inflammatory response of SCD patients, contributing to an improved quality of life. This study aimed to evaluate the effect of a regular physical exercise program on the anti-inflammatory responses in SCD patients. A non-randomized clinical trial was conducted in adult SCD patients. The patients were divided into two groups: 1-Exercise Group, which received a physical exercise program three times a week for 8 weeks, and; 2-Control Group, with routine physical activities. All patients underwent the following procedures initially and after eight weeks of protocol: clinical evaluation, physical evaluation, laboratory evaluation, quality of life evaluation, and echocardiographic evaluation. Comparisons between groups were made using Student's t-test, Mann-Whitney test, chi-square test, or Fisher's exact test. Spearman's correlation coefficient was calculated. The significance level was set at p < 0.05. There was no significant difference in inflammatory response between the Control and Exercise Groups. The Exercise Group showed an improvement in peak VO2 values (p < 0.001), an increase in the distance walked (p < 0.001), an improvement in the limitation domain due to the physical aspects of the 36-Item Short Form Health Survey (SF-36) quality of life questionnaire (p = 0.022), and an increase in physical activity related to leisure (p < 0.001) and walking (p = 0.024) in the International Physical Activity Questionnaire (IPAQ). There was a negative correlation between IL-6 values and distance walked on the treadmill (correlation coefficient -0.444, p = 0.020) and the estimated peak VO2 values (correlation coefficient -0.480; p = 0.013) in SCD patients in both groups. The aerobic exercise program did not change the inflammatory response profile of SCD patients, nor did it show unfavorable effects on the parameters evaluated, and patients with lower functional capacity were those with the highest levels of IL-6.

Clinicopathological analysis and specific discriminating markers of interleukin detection in cerebrospinal fluid with primary central nervous system lymphoma: results from a retrospective study.

Primary central nervous system lymphoma (PCNSL) is special extranodal malignant non-Hodgkin lymphomas. This study analyzed clinical features and prognostic factors of PCNSL and evaluated the difference of interleukin (IL) concentrations incerebrospinal fluid (CSF) between PCNSL and systemic non-Hodgkin lymphoma (sNHL). Patients consecutive newly diagnosed with PCNSL were recruited, the demographic and clinicopathological data were retrospectively analyzed, and the potential prognostic factors for overall survival (OS) were identified with survival analysis. 27 patients with PCNSL and 21 patients with sNHL collected CSF IL-5, IL-6, and IL-10 concentrations at diagnosis. The difference in interleukin (IL) concentrations in two diseases was analyzed to evaluate the value of IL concentrations. A total of 64 patients with PCNSL were enrolled, the median age was 54.50years (range 16-85years); male: female ratio was 1.91. Headache was the most common complaint symptom involved in 42.19% (27/64) of patients. Diffuse large B-cell lymphoma (DLBCL) accounted for 89.06% (57/64) of patients; other uncommon types accounted for 3.13% (2/64). In prognostic analysis, multiple lesions and Ki67 ≥ 75% expression exhibited a worse prognosis(P = 0.041), and patients with autologous hematopoietic stem cell transplantation (auto-HSCT) treatment presented superior OS (P < 0.05). In multivariate analysis, BCL2 expression was revealed as an unfavorable prognostic marker, and auto-HSCT was revealed as a favorable prognostic marker. CSF IL-10 concentration in patients with PCNSL was significantly higher than sNHL (P = 0.000) and excluded other histopathology of NHL; IL-10 value was still significantly different between DLBCL of PCNSL and sDLBCL (P = 0.003). In ROC curve analysis, the cutoff value of IL-10 was 0.43pg/mL for the diagnosis value of PCNSL, sensitivity was 96.3%, specificity was 66.67%, and AUC was 0.84 (0.71-0.96). Although IL-6 concentration did not differ in the two groups, IL-10/IL-6 ratio was meaningful, with a cutoff value of 0.21, sensitivity of 81.48%, specificity of 80.95%, and AUC of 0.83 (0.71-0.95). This study highlights the characteristics of patients with PCNSL, potential prognostic makers also have been explained. CSF interleukin (IL) concentrations revealed IL-10 levels, and IL-10/IL-6 ratio may represent a useful biomarker in the differential diagnosis of PCNSL and sNHL.

Indicators of the cytokine system in practically healthy women of different ages and interrelation with the emotional state

Numerous studies show the role of the cytokine network in the pathogenesis of anxiety and depression. However, at present, studies of the correlation between the levels of pro-inflammatory and antiinflammatory cytokines and the level of emotional stress are rather few. The aim of the study was to analyze the serum levels of pro-inflammatory and anti-inflammatory cytokines and the emotional state in apparently healthy women depending on age. Serum levels were tested IL-1β, IL-6, IL-17, IFNγ, IL-10 and IL-4 in 100 apparently healthy women, who were divided into 3 groups depending on age (WHO): 18-44 (young age) 30 people, 45-59 (middle age) 40 people, 60-74 (old age) 30 people (sandwich variant of enzyme-linked immunosorbent assay, pg/mL). To assess the emotional component of health, all the subjects passed the questionnaire SF-36 “Assessment of the quality of life”. Statistical processing of the obtained data was carried out using the analytical software IBM SPSS Statistics, 22.0. In practically healthy women, an increase in the values of IL-1β and IL-6 was found in the elderly group (p &lt; 0.05), while no differences were found between the groups of young and middle age. The level of IFNγ in all age groups of women did not differ significantly. At the same time, in the elderly group, the levels of IFNγ in 40% ranged from 1.04 to 8.76 pg/mL, and in 60% of women – from 24.85 to 28.5 pg/mL. IL-17 was also high (p &lt; 0.05-0.01) in the group of women aged 60-74. In the anti-inflammatory link, the opposite picture was observed, for example, in young and middle-aged women, the levels of IL-10 and IL-4 were higher than in the elderly group. Thus, the analysis made it possible to state that the parameters of the cytokine profile and emotional state in women are associated with age.

Moderate physical exercise and immune system modulation in patients with breast cancer treated with neoadjuvant chemotherapy.

605 Background: The link between physical activity (PA) and immune system is known. However, are not clearly understood which mechanisms are activated by PA. We investigated the effect of moderate PA (MPA), on a panel of circulating cytokines during neoadjuvant chemotherapy (CT) in patients (pts) with breast cancer. Methods: Pts received sequential epirubicin and cyclophosphamide for 4 cycles followed by weekly paclitaxel ± trastuzumab. MPA consisted of Nordic or fit walking, 3 workouts/week, 1 hour each, in the 9 weeks before Surgery (S). Blood samples were collected in pts underwent MPA (TR) and in a group of pts who declined MPA (UN) at baseline (T0), at day 1 of week 6 of paclitaxel (starting MPA) (T1) and before S (T2). At each time point the level of 22 cytokines (IL1b, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL15, IL17a, IL18, IL21, CCL2, CCL4, CXCL10, CCL22, IFNγ, TGFβ, TNFα, VEGF) was measured using Simple Plex Ella. Sample size was calculated using effect size method considering a Cohen’s d of 0.65 as observed for a candidate cytokine (IL-6) between two groups. Considering a desired statistical power of 0.8 and a probability level of 0.05 a minimum of 78 patients were required. The difference among the median value of cytokines was analysed using non parametric Mann Whitney U test. Comparisons between time points in the same group were analysed with Wilcoxon signed-rank test. Results: Accrual is completed. 61 pts were TR and 20 UN. Main patients’ characteristics are listed. At T0 IL4, IL17, IL18 and VEGF level was significantly higher in UN respect to TR pts. At T1 IL4, IL17 and IL18 level remained significantly higher in UN pts. At T2, UN pts showed significantly higher value of IL4, IL6, IL7, IL8, IL17, IL18 VEGF and TGFβ. IL21 was significantly higher in TR pts. Longitudinal analysis between T0 and T1 in TR and UN pts showed significantly lower level of CCL22 and significantly higher level of IL7, IL13 and CXCL10 in TR pts and significantly higher level of IL8 in UN pts. Longitudinal analysis between T1 and T2 showed significantly higher level of IL21, CXCL10, CCL22, TNFα and significantly lower level of IFNγ, IL6, IL8, CCL2, TGFβ in TR pts and significantly lower level of CXCL10 in UN pts. Conclusions: TR and UN pts differed modestly at baseline including acceptance of MPA. The longitudinal analysis T0-T1 showed that CT induced more evident changes in TR than in UN pts. Longitudinal analysis T1-T2 demonstrated major changes in Th1 and Th2 cytokines only in TR pts. Overall, CT induced weak changes in UN and greater changes in TR pts strengthened by the addition of MPA. These observations suggest a more efficient immune system in TR pts and a possible additional benefit derived from MPA. [Table: see text]

Clinical value of RANKL, OPG, IL-6 and sclerostin as biomarkers for fibrous dysplasia/McCune-Albright syndrome.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic bone disease caused by a somatic mutation in the GNAS gene. Currently used bone turnover markers (BTMs) do not correlate with the clinical picture and are not useful to predict or monitor therapy success. This study assessed the correlation of RANKL, OPG, RANKL/OPG ratio, IL-6 and sclerostin with the classic BTMs alkaline phosphatase (ALP), procollagen type 1 propeptide (P1NP) and beta crosslaps (CTX), with pain, skeletal burden score (SBS) and response to bisphosphonate or denosumab treatment. Ninety-six serum samples of adult patients >18years of age with any subtype of FD/MAS were included from the biobank facility of the Leiden University Medical Center, Center for Bone Quality between 2015 and 2021. Standard laboratory assessments were assessed as part of usual care. The concentrations of potential biomarkers RANKL, OPG, sclerostin, IL-6 were analyzed. Data on FD/MAS subtype, age, pain, treatment history and treatment response were retrieved from the electronic patient files. Baseline characteristics were summarized by descriptive statistics. Correlations of the concentrations of the potential biomarkers with classic bone turnover markers, SBS and pain scores were cross-sectionally assessed by Spearman rank order correlation. Correction for multiple testing was performed by Benjamini and Hochberg False Discovery Rate. A sensitivity analyses was performed by excluding patients with SBS below 15 and patients using antiresorptive medication at the time of blood withdrawal or within the wash-out period. In patients treated with bisphosphonates or denosumab after blood withdrawal, pre-treatment concentrations were compared in patients with and without therapy response by Mann Whitney U test. The median age of the patients was 41.2 (Q1-Q3 25.9-52.2) years, 62.5% was female. Median SBS was 2.5 (Q1-Q3 0.5-7.8). RANKL level correlated weakly with ALP (Spearman rho 0.309, p=0.004, n=84), but not with P1NP or CTX. The RANKL/OPG ratio, OPG, IL-6 and sclerostin did not correlate with ALP, P1NP or CTX. None of the potential biomarkers correlated with SBS or pain. Results of the sensitivity analyses were comparable. Pre-treatment biomarker levels were similar in patients with and without improvement in pain scores following bisphosphonate therapy. Pre-treatment RANKL and sclerostin were comparable between patients with and without improvement in pain scores after denosumab therapy. Pre-treatment IL-6 level and the RANKL/OPG ratio seemed to be higher in patients with response to denosumab (IL-6: median 0.64 (Q1-Q3 0.53-0.74) pg/mL, n=6, RANKL/OPG: median 0.062 (Q1-Q3 0.016-0.331), n=5) compared to patients without response (IL-6: median 0.35 (0.20-0.54) pg/mL, n=5, RANKL/OPG: 0.027 (0.024-0.046), n=4). Pre-treatment IL-6 correlated with the improvement in maximum pain scores (rho 0.962, p<0.001, n=9) and average pain scores (rho 0.895, p=0.001, n=9) reported during denosumab therapy. Increased concentrations of RANKL, IL-6, sclerostin and of the RANKL/OPG ratio do not indicate severity of FD/MAS, as no correlation was observed of these potential biomarkers with the classic BTMs and SBS. Biomarker levels did not correlate with pain and had no value in predicting bisphosphonate treatment response. These biomarkers are not superior over the currently used methods of assessing ALP, P1NP and CTX or evaluating SBS to establish disease extent or activity and provide no reliable results. Yet, possibly pre-treatment IL-6 and the RANKL/OPG ratio may have some predictive value for clinical response to denosumab. Therefore, studies investigating disease activity and treatment response should include lesional imaging and patient-reported outcome measures.

Identification of prognostic biomarkers in plasma of patients with metastatic urothelial carcinoma (mUC).

e16564 Background: Performance status and visceral metastasis before first-line chemotherapy based on cisplatin (CDDP) predict survival of subjects with mUC. The objective of this study was to explore the prognostic value of selected plasma biomarkers. Methods: We have evaluated the samples from 86 mUC subjects (64.0% males). Performance status of ECOG 2 and visceral metastasis were present in 39.5% and 50.0% cases, respectively. The MILLIPLEX panels were used for determination of 51 biomarkers in plasma taken from patients before systemic therapy initiation. Study population was dichotomized into high and low groups by median for each parameter. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was carried out by the Cox regression model. Results: At median follow-up of 8.6 months (6.4-10.1), 95.3% of patients experienced disease progression and died. Better PFS was associated with low levels of nine biomarkers: IL-1RA (HR 0.65, P=0.0425), IL-6 (HR 0.52, P=0.002), IL-8 (HR 0.46, P=0.0002), IL-10 (HR 0.49, P=0.0004), IL-15 (HR 0.61, P=0.0198), IL-22 (HR 0.45, P=0.0043), MCP-1 (HR 0.59, P=0.0147), M-CSF (HR 0.59, P=0.0119), and VEGF-A (HR 0.64, P=0.0392). OS was significantly better in patients with low levels of G-CSF (HR 0.42, P=0.047), IL-1RA (HR 0.63, P=0.0314), IL-2 (HR 0.61, P=0.0249), IL-6 (HR 0.47, P=0.004), IL-8 (HR 0.44, P=0.0001), IL-10 (HR 0.43, P&lt;0.0001), IL-15 (HR 0.53, P=0.0026), IL-22 (HR 0.47, P=0.0065), IL-27 (HR 0.63, P=0.0343), MCP-1 (HR 0.59, P=0.0134), M-CSF (HR 0.55, P=0.0042), TNFα (HR 0.53, P=0.0024), and VEGF-A (HR 0.59, P=0.0124). The independent prognostic values of IL-6, IL-10, MCP-1, M-CSF, and TNFα were confirmed in a multivariate analysis. Conclusions: In this study, we have proved that selected plasma biomarkers may have a prognostic value in mUC patients. Further research is required to understand their role as the biomarkers, but also potentially treatable pathogenic factors for mUC development. This research was funded by grant of the Integrated Infrastructure Operational Program, ITMS: 313011AFG5, co-financed by the European Regional Development Fund &amp; OncoReSearch, Slovakia.

Immunological Pathways in the Development of Postoperative Hyperamylasemia and Postoperative Pancreatitis – Preliminary Results

Postoperative pancreatitis complications can be separated into two main groups based on literature reviews and clinical and experimental trials. Some authors suggest that postoperative pancreatitis is a severe complication that should be treated conservatively and operatively if needed. Other authors defend an opposite opinion that only postoperative hyperamylasemia exists, which is a transitory condition with no risk of complications.&#x0D; At “Alexandrovska” University Hospital for Active Treatment, Clinic of General and Liver-Pancreatic Surgery, a cohort of patients with increased amylase concentrations in the postoperative period between January 2017 and December 2018 were studied and followed with immunological and biochemical tests for interleukin (IL)-6. Regardless of the type of surgery to which they were subjected, all patients who presented with an elevated amylase concentration in the postoperative period were selected. The working hypotheses were the following: i) IL-6 is directly relevant in the development of postoperative pancreatitis; ii) the concentration of IL-6 is a prognostic factor in the early postoperative period and marks the boundary at which patients will develop postoperative pancreatitis and its various clinical manifestations; and iii) the postoperative period is accompanied by transient postoperative hyperamylasemia and absence of complications. To test these hypotheses, the values of IL-6 were statistically analyzed using SPSS v23 software.&#x0D; The results show that, with a 95% confidence interval (CI), a statistically significant difference is found in the concentration of IL-6 in patients who developed postoperative pancreatitis versus those with transient hyperamylasemia.&#x0D; The present study shows a direct link between the immunological marker, IL-6, and the course of both postoperative pancreatitis and transient hyperamylasemia, making this marker valuable in elucidating the differences in the development of postoperative pancreatitis and transient hyperamylasemia in the early postoperative period. Thus, IL-6 can be used to reach the correct diagnosis and decide effective treatment.