Interleukin-6 In Patients Research Articles

Elevated Level of Serum Interleukin-21 and Its Influence on Disease Activity in Anti-Neutrophil Cytoplasmic Antibodies Against Myeloperoxidase-Associated Vasculitis.

Interleukin-21 (IL-21) has been shown to play an important role in the immune system. This study aimed to investigate the changes in the level of IL-21 in patients with anti-neutrophil cytoplasmic antibodies against myeloperoxidase (MPO-ANCA)-associated vasculitis (MPO-AAV), as well as explore its influence on disease activity and the potential mechanism. Flow cytometry was performed to detect the percentage of follicular helper T cells (Tfh) among CD4+T cells (Tfh%); the percentage of Tfh-expressing inducible costimulator (ICOS) among Tfh cells (ICOS+Tfh%); the percentage of Tfh-expressing programmed cell death protein 1 (PD-1) among Tfh cells (PD-1+Tfh%); and mean fluorescence intensity of Tfh-expressing ICOS or PD-1 in the peripheral blood. An enzyme-linked immunosorbent assay was used to measure the levels of serum IL-21 and MPO-ANCA. The Birmingham Vasculitis Activity Score was used to evaluate disease activity. Our results revealed that the level of IL-21 in the patient group was significantly higher than that in the healthy control group (1324.2 ± 125.3 pg/mL vs. 704.2 ± 41.1 pg/mL, P < 0.001), and it was an independent factor affecting the disease activity (P = 0.022). Thus, blocking the activity of IL-21 may represent a potential novel target for the future treatment of MPO-AAV.

CORRELATIONS BETWEEN PERIPHERAL BLOOD INFLAMMATORY MARKERS AND INTERLEUKIN-21 IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

Inflammation that occurs in the tumor microenvironment and in the systemic circulation correlates with disease progression and prognosis in a number of tumors. One way to assess the systemic immune response is to determine the cells/their ratio associated with inflammation, which can easily be measured with complete blood count. IL-21 has a variety of regulatory effects on both normal and tumor cells, leading to their proliferation, differentiation, and apoptosis.The aim of our study was to determine the level of IL-21 in patients with lymphoma-leukemia and to correlate it with the biomarkers of systemic inflammation involved in carcinogenesis - NLR, PLR, PMR, HLR, SII, dNLR.The study included patients with hematologic tumors who underwent splenectomy for therapeutic indications. The control group consisted of patients who also underwent splenectomy but not due to malignant tumor or autoimmune disease.According to our study analysis interleukin-21 levels did not differ significantly between the study and control groups. Serum levels of interleukin-21 in patients with malignant hematologic tumors are negatively correlated with dNLR.

Plasma Interleukin-33 Cannot Predict Hip Osteonecrosis in Patients With Sickle Cell Disease: A Case-Control Study

BackgroundPlasma interleukin-33 (IL-33), a cytokine associated with inflammatory and autoimmune disease, has been described to be significantly raised in osteonecrosis of the femoral head (ONFH) and hence was recommended for use as a marker for ONFH. The concentration of plasma interleukin-33 level has not been estimated in any studies conducted in patients with sickle cell disease (SCD); hence, we investigated the levels of plasma interleukin-33 in patients with sickle cell disease with or without ONFH to assess whether it can be used as a marker for the early detection of ONFH in this disease also.MethodsForty-four consecutive patients with sickle cell disease with osteonecrosis of the femoral head and matched controls without ONFH were evaluated for plasma interleukin-33 levels by enzyme-linked immunosorbent assay (ELISA). All patients were confirmed for sickle cell disease using high-performance liquid chromatography (HPLC). ONFH was diagnosed in patients with sickle cell disease using clinical-radiological findings. Univariate and multivariate analyses were performed using the IL-33 level as the dependent variable.ResultsPlasma IL-33 levels were comparable in 44 patients with sickle cell disease with osteonecrosis of the femoral head as compared with 24 patients with sickle cell disease without ONFH (2.05 ± 4.57 pg/mL versus 1.50 ± 2.89 pg/mL, p-value = 0.590). There was no significant difference in IL-33 levels in different stages of avascular necrosis (AVN).ConclusionsPlasma interleukin-33 levels cannot act as a marker of ONFH as were being considered in idiopathic ONFH or ONFH caused by other causes such as trauma and chronic steroid or alcohol usage.

Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents

BackgroundThrough regulation of signaling pathways, microRNAs (miRNAs) can be involved in sepsis and associated organ dysfunction. The aims of this study were to track the 7-day time course of blood miRNAs in patients with sepsis treated with vancomycin, gentamicin, or a non-nephrotoxic antibiotic and miRNA associations with neutrophil gelatinase-associated lipokalin (NGAL), creatinine, procalcitonin, interleukin-6, and acute kidney injury (AKI) stage.MethodsOf 46 adult patients, 7 were on vancomycin, 20 on gentamicin, and 19 on another antibiotic. Blood samples were collected on days 1, 4, and 7 of treatment, and miRNAs were identified using quantitative reverse transcription PCR.ResultsThe results showed no relationship between miRNA levels and biochemical variables on day 1. By day 7 of gentamicin treatment miR-15a-5p provided good discrimination between AKI and non-AKI (area under curve, 0.828). In patients taking vancomycin, miR-155-5p and miR-192-5p positively correlated with creatinine and NGAL values, and miR-192-5p and miR-423-5p positively correlated with procalcitonin and interleukin-6 in patients treated with a non-nephrotoxic antibiotic. In patients together we found positive correlation between miR-155-5p and miR-423-5p and all biochemical markers.ConclusionThe results suggest that these four miRNAs may serve as diagnostic or therapeutic tool in sepsis, renal injury and nephrotoxic treatment.Trial registrationClinicalTrials.gov, ID: NCT04991376. Registered on 27 July 2021.

Effects of sample handling on the stability of interleukin-6 in patients with breast neoplasms

Abstract Objectives To investigate the influence of preservation methods and processes on the plasma interleukin-6 (IL-6) stability. Methods Lithium-heparin plasma was collected from female patients: 32 female patients with invasive breast neoplasms and 20 healthy females. Each sample was divided into three tubes. Samples were stored at different temperatures or at different times. The concentration of IL-6 was detected. Results IL-6 levels in patients were not altered significantly compared to the control group after storage at 4 °C or 25 °C for 12 h. However, IL-6 levels were significantly higher compared to controls (p&lt;0.05) after storage at 25 °C for 48 h. IL-6 levels in patients with breast neoplasms were significantly higher compared to the control group (p&lt;0.05) when stored at 4 °C after 12 h. IL-6 levels in patients with breast neoplasm increased more than 10-folds compared to the control group after only 2 h storage at 25 °C. Conclusions Concentrations of IL-6 in breast neoplasms samples significantly change under different storage conditions. Pretreatment needs to be standardized for blood sample handling procedure. Comparison of different storage conditions of IL-6 levels may not be reliable.

Effect of nonsurgical periodontal therapy on gingival crevicular fluid levels of Interleukin-35 in patients with periodontitis

ObjectiveInterleukin (IL)-35 is a comparatively novel immunosuppressive cytokine produced by T-regulatory cells, the purpose of which in periodontal well being and disease still eludes the researchers. This study intends to measure and compare the levels of IL-35 in gingival crevicular fluid (GCF) taken from periodontitis patients before and at first, second and third week post non-surgical periodontal therapy. Methodologyology: Twenty patients having generalized chronic periodontitis (mean age of 36.25 ± 5.12 years) with moderate to severe disease were assessed clinically for the following parameters: plaque index, gingival index, probing pocket depth, and clinical attachment loss. GCF samples were collected from deepest pockets before performing a full mouth non-surgical periodontal therapy. GCF samples were again collected at 1st, 2nd, and 3rd week after non-surgical periodontal therapy and, IL-35 levels in the GCF samples were measured using an ELISA kit. ResultsAll the clinical parameters improved significantly over time from baseline to 3rd week. The results for plaque index, gingival index, and probing pocket depth were highly significant (p < 0.001) and significant (p < 0.05) for clinical attachment loss. The IL-35 concentration in GCF increased post periodontal therapy from baseline till third week and results were statistically highly significant (p < 0.001). A significant negative correlation (p < 0.001) was found between clinical parameters and IL-35 levels. ConclusionsWith the healing of the previously diseased periodontal tissues, the levels of IL-35 in GCF increases significantly. Therefore, IL-35 can be considered as potential inflammatory marker of periodontal health and disease.

Gene characterization of extended-spectrum-β-lactamase producing Klebsiella pneumoniae isolates and analysis of interleukin-11 in patients with urinary tract infection

Cross-sectional and case-control study was conducted on 587 patients with urinary tract infection (UTI) to determine prevalence of Klebsiella pneumoniae and three extended-spectrum-β-lactamase (ESBL) genes (blaSHV, blaTEM and blaCTX-M). Besides, IL-11 serum level was determined to predict its biomarker significance in patients with ESBL-producing K. pneumoniae (K-ESBLs). Ninety-three K. pneumoniae isolates were identified (15.8%), and 64 (68.8%) of these isolates were K-ESBLs, which showed a high prevalence of resistance against 12 antibiotics out of 16. PCR analysis of K-ESBLs revealed that blaSHV gene was prevalent in all isolates (100.0%), while blaTEM gene was detected in 35 isolates (54.7%). blaCTX-M gene was found in only two isolates (3.1%). IL-11 levels were significantly elevated in K-ESBL and K-non-ESBL patients compared to controls (52.4 ± 21.8 and 34.5 ± 18.8 vs. 6.3 ± 4.2 pg/mL, respectively; p-value <0.001), but it is noteworthy that IL-11 levels were significantly higher in K-ESBL patients than in non-ESBL patients (p-value <0.001) (Fig. 1). ROC curve analysis revealed that IL-11 was a significant predictor of K-ESBLs in patients with UTI. This cytokine occupied an excellent AUC, which was 1.0. At a cut-off value of 11.1 pg/mL, the sensitivity and specificity of IL-11 were 100.0%. In conclusion, the study demonstrated the significance of K-ESBLs in the development of UTIs, and this uropathogen showed a high level of multidrug resistance, as well as a high frequency of blaSHV and blaTEM genes. Besides, IL-11 may have emerged as a significant indicator of UTIs caused by K-ESBLs.

The level of interleukin-17, 23, and gamma interferon in cutaneous leishmaniasis patients before and after intra lesion treatment.

Leishmaniasis is a zoonotic vector-borne disease that is endemic in tropical and sub-tropical districts. The immune system response is one of the most important factors that has affected parasitic treatment. In this research, the production of IL-17 (Interleukin 17), IL-23 (Interleukin 23), and IFN-ɤ (Interferon-gamma) in peripheral blood mononuclear cells (PBMCs) isolated from patients with cutaneous leishmaniasis caused by L. major before and after treatment were compared to evaluate their roles in the recovery process. For this experimental study, we recruited 23 patients in Iran. Ten milliliters of peripheral blood samples were collected before and after one month of treatment, and PBMCs were isolated. Production of IL-17, IL-23, and IFN-ɤ was assessed by sandwich ELISA technique. The production of IFN-ɤ and IL-17 in patients (before treatment sensitive leishmaniasis and resistance leishmaniasis) was more than the healthy controls (P < 0.05). Moreover, both of the cytokines productions in sensitive leishmaniasis cases were more than the resistance leishmaniasis patients. In this study, we observed lower levels of IL-23 in patients compared to healthy controls. And among the patients, IL-23 production was lower in sensitive leishmaniasis cases (P < 0.05). Conclusion: It appears that the production of IFN-ɤ is necessary for the treatment of leishmaniasis, but further studies are required to address the role of IL-17 and IL-23 in this disease.

Diagnosis of intraamniotic inflammation by measuring vaginal interleukin-6 in patients with cervical insufficiency: could amniocentesis be avoided?

Background Cervical insufficiency is a recurrent, passive, and painless dilation of the cervix in the second trimester. The etiology is unclear, but there may be an association with subclinical intraamniotic infection. Interleukin-6 (IL-6) production in the amniotic cavity is induced by bacterial invasion, it is the major proinflammatory cytokine released in response to infection. Although the gold standard method to measure it is through an amniocentesis, the procedure constitutes an invasive technique with several associated risks. The objective of this study is to determine if there is a correlation between intraamniotic and vaginal IL-6 in patients with cervical insufficiency and bulging membranes during the second trimester of pregnancy, in order to avoid an amniocentesis before the rescue cerclage. Methods A cohort study was performed in which all patients with cervical insufficiency and bulging membranes admitted into our tertiary hospital between 2019 and 2020 were included, and a control group of asymptomatic women in the second trimester of gestation where studied at the same time. Patients with bulging membranes underwent an amniocentesis to quantify amniotic IL-6, and a sample of vaginal fluid for vaginal IL-6 determination was obtained from both the study and the control group. Results A total of 20 women were included in each group. Median gestational age at diagnosis was 22 weeks in patients with bulging membranes, and 21 weeks in the control group. Vaginal IL-6 in control group (10.875 pg/mL) is much lower than the study group one (1308.77 pg/ml). In patients with bulging membranes, vaginal IL-6 expression was lower in the vagina than in the amniotic cavity [average IL-6 in the amniotic cavity 26890.07 pg/mL, vs 1308.77 pg/mL in the vagina (p < .01)]. Through a Spearman coefficient correlation rank [rho = 0.709 (p < .001)], there is a positive correlation between amniotic and vaginal IL-6 values. The best value of this correlation was calculated with the ROC curve, being the area under the curve 0.929 (CI 95% 0.721–0.995), and the cutoff of point less than 61.4 pg/ml (sensitivity 83.33%; specificity 92.86%). Patients with vaginal IL-6 < 61.4 pg/ml associated a longer latency time between diagnosis and delivery, a higher neonatal weight and a lower perinatal mortality. Rescue cerclage in vaginal IL-6 < 61.4 pg/ml was the best predictor of good pregnancy outcome. Conclusion There is a correlation between intraamniotic and vaginal IL-6 in patients with cervical insufficiency and bulging membranes during the second trimester of pregnancy. However, further studies are needed in order to considerate the avoidance of an amniocentesis before an emergency cerclage.

The frequencies of peripheral blood CD5+CD19+ B cells, CD3\u2212CD16+CD56+ NK, and CD3+CD56+ NKT cells and serum interleukin-10 in patients with multiple sclerosis and neuromyelitis optica spectrum disorder

BackgroundMultiple sclerosis (MS) and neuromyelitis optica syndrome disease (NMOSD) are inflammatory diseases of the central nervous system. The pathogenesis and treatments for these two conditions are very different. Natural killer (NK) and natural killer T (NKT) cells are immune cells with an important role in shaping the immune response. B cells are involved in antigen presentation as well as antibody and cytokine production. There is conflicting evidence of the roles of NK, NKT, and B cells in the two conditions. We aimed to compare the frequency of CD3−CD16+CD56+NK, CD3+ CD56+ NKT, and CD5+CD19+ B cells in the peripheral blood and serum Interleukin-10 (IL-10) in patients with MS and NMOSD.MethodsCD19+CD5+ B, CD3− CD16+CD56+ NK, and CD3+CD56+ NKT cells were quantitated by flow cytometry in 15 individuals with Interferon-Beta (IFN-β) treated relapsing–remitting MS (RRMS), 15 untreated RRMS, and 15 NMOSD patients as well as 30 healthy controls (HC). Serum IL-10 was measured using an enzyme-linked immunosorbent assay (ELISA).ResultsThe percentage of CD3−CD56+CD16+ NK cells in the peripheral blood of IFN-treated MS (1.81 ± 0.87) was significantly lower than for untreated RRMS (4.74 ± 1.80), NMOSD (4.64 ± 1.26) and HC (5.83 ± 2.19) (p < 0.0001). There were also differences for the percentage of CD3−CD16+ and CD3−CD56+ cells (p < 0.001 and p < 0.0007; respectively). IFN-treated RRMS (2.89 ± 1.51) had the lowest proportion of CD3+CD56+ among the study groups (p < 0.002). Untreated RRMS (5.56 ± 3.04) and NMOSD (5.47 ± 1.24) had higher levels of CD3+CD56+ than the HC (3.16 ± 1.98). The mean percentage of CD19+CD5+ B cells in the peripheral blood of untreated RRMS patients (1.32 ± 0.67) was higher compared to the patients with NMOSD (0.30 ± 0.20), HC (0.5 ± 0.22) and IFN-treated RRMS (0.81 ± 0.17) (p < 0.0001). Serum interleukin-10 was significantly higher in the IFN-treated RRMS (8.06 ± 5.39) and in HC (8.38 ± 2.84) compared to untreated RRMS (5.07 ± 1.44) and the patients with NMOSD (5.33 ± 2.56) (p < 0.003).ConclusionsThe lower proportion of CD3−CD56+ CD16+ NK and CD3+CD56+ cells in peripheral blood of IFN-treated RRMS compared to other groups suggests the importance of immunomodulation in patients with RRMS disorder. Based on the differences in CD19+CD5+ B cells and serum IL-10 between patients and HC, supplementary assessments could be of value in clarifying their roles in autoimmunity.

Effects of the Treatment of Dong Medicine Five-Flavour Anti-Diarrhoea Soup Combined with Melalazine on Serum Complement C3, C4, Interleukin-23 and Interleukin-17 in Patients with Ulcerative Colitis

To investigate the clinical effect of the treatment of dong medicine five-flavor anti-diarrhea soup combined with melalazine on the chronic recurrence type (spleen deficiency and dampness accumulation type) ulcerative colitis. A total of 60 patients conforming to the diagnostic criteria of traditional Chinese and Western medicine in the anorectal department and gastroenterology department of the First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine from September 2019 to December 2020 were randomly selected and grouped. Patients in the treatment group took dong medicine five-flavor anti-diarrhea soup combined with melalazine enteric tablets (30 patients). Patients in the control group received oral melalazine intestinal-soluble tablets (30 patients). Changes in the traditional Chinese medical syndrome scores, Baron endoscopic scores, Mayo scores, serum complement C3 and C4, serum interleukin-23 and interleukin-17 were recorded before and after 8 w of treatment in the treatment and control groups, and total traditional Chinese medicine symptoms were observed and recorded. The treatment group was better than the control group in improving the total points of traditional Chinese medical symptoms, Mayo and Baron scores and reducing complement C3 and C4 and serum interleukin-23 and interleukin-17 levels, which were demonstrated as statistically significant (p<0.05). The treatment effects of dong medicine five-flavor anti-diarrhea soup combined with melalazin on the chronic recurrence type (spleen deficiency and dampness accumulation type) ulcerative colitis of the treatment group are better that of the control group regarding the Mayo scores, Baron endoscopic scores, remission of various symptoms of traditional Chinese medicine, reduction of serum complement and C3, C4, interleukin-23 and interleukin-17 levels.

Increased serum levels of interleukin-17 in patients with alopecia areata and non-segmental vitiligo.

IntroductionAlopecia areata (AA) and vitiligo are both skin diseases of autoimmune origin. AA is characterized by patchy hair loss primarily on the scalp but may involve other areas as well, while vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body. Many facts indicate similar pathogenesis of these diseases. Both dermatoses are associated with frequent coexistence of other autoimmune diseases and share common genetic risk factors. Recent data support the theory of the involvement of IL-17 in the pathogenesis of both AA and vitiligo.AimTo evaluate and compare the serum levels of interleukin (IL)-17 in patients with AA and non-segmental vitiligo (NSV). To assess whether the pattern of serum cytokine concentration can be associated with clinical details and activity of the disease.Material and methodsA cross-sectional study was conducted on 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of IL-17 were determined quantitatively by ELISA method.ResultsOur analysis identified a systemic inflammatory signature associated with AA and NSV, characterized by elevated levels of IL-17. The levels of IL-17 did not differ significantly between AA patients and NSV patients.ConclusionsOur results show that AA and vitiligo may share common etiopathogenetic pathways, which suggests the potential of developing targeted therapies for both AA and vitiligo treatment. Imbalance of T cell subpopulations and complex systemic cytokine profiles may contribute to the pathogenesis of AA and vitiligo.

Functional and biochemical improvement following total knee arthroplasty in early postoperative period.

There are very few studies about total knee arthroplasty biomechanical and biochemical effects in the early postoperative period. The aim of this study was to investigate the effect of total knee arthroplasty on pain intensity, knee joint valgus angle, malalignment, functional status, knee joint position sense, and cytokine levels. A total of 29 patients (female/male: 24/5) who underwent total knee arthroplasty were included in the late-stage knee osteoarthritis group, and 22 patients (female/male: 13/9) with grade 4 osteoarthritis were included in the early-stage knee osteoarthritis group. The visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index were used to evaluate the pain intensity and functional status. Alignment and knee position sense measurements were also calculated. Systemic venous blood samples were taken to evaluate the interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta cytokine levels. In the study group, there were positive improvements in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 70° knee flexion angle parameters, and interleukin-6 of patients at the postoperative 6th week compared to the preoperative period (p<0.05). The patients in the study group had similar or better results in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 35°, 55°, and 70° knee flexion angles parameters, and in interleukin-6, compared to the control group at postoperative 6th week. Total knee arthroplasty provides improvements in pain, function, valgus angle, joint position sense, and interleukin-6 in the early postoperative period.

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

Correlation of inflammatory cytokine Interleukine (IL-4) and Matrix metalloproteinase-9 in chronic obstructive pulmonary disease (COPD)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) presents with respiratory symptoms caused by airflow obstruction. Parenchymal abnormalities, constricted airway and inflammation are major causative factors associated with COPD. Proteases such as matrix metalloproteinases (MMP) and a pleiotropic cytokine Interleukin-4 (IL-4) play an important role in lung tissue remodeling. However, there is a dearth in studies correlating the levels of MMP9 and IL-4 in patients of COPD. This study aims to evaluate the serum levels of MMP-9 and IL-4 in COPD and correlate with clinical characteristics of COPD patients. Materials and methods: This case control study pre-screened 134 participants of which 40 were healthy and 94 were COPD patients from the Department of Pulmonary Medicine at the Prasad Institute of Medical Sciences Lucknow. Results: Significantly increased level of Serum MMP-9 (212.6 ± 75.5 ng/ml) were detected in COPD group as compared to the control group (97.5± 45.6 ng/ml). Also, the IL-4 levels were significantly different in the control group Conclusions: Detection of higher levels of MMP9 and IL-4 in patients suffering from COPD in the present study implies that these biomarkers could serve as markers for understanding the depth of COPD development and therapy. Keywords: Matrix metalloproteinases (MMP), Interleukin-4 (IL-4), COPD

Elevated IL-37 Serum Levels in Patients with Transitional Cell Carcinoma of Bladder.

Interleukin-37 (IL-37) is a recently described cytokine that emerges as a natural inhibitor of inflammatory and immune responses. However, IL-37 has not yet been investigated in bladder cancer, and its biological role is unknown. The purpose of this study was to investigate IL-37 serum levels in patients with bladder cancer and determine whether they were linked to the patients' pathological characteristics. IL-37 serum levels were measured using a commercial ELISA kit in 60 patients with transitional cell carcinoma (TCC) of the bladder (mean age: 64.55±12.93) and 50 healthy controls (mean age: 62.94±12.69). Non-parametric tests were used for statistical comparisons, and the Cohen's d effect size was calculated to evaluate the practical and clinical significance of the results. Our findings indicated an increasing trend in IL-37 serum levels in patients with TCC (42.77±3.36 pg/ml) in comparison with controls (40.51±7.32 pg/ml, p=0.09). However, IL-37 serum levels were found to be significantly higher in male patients (44.72±3.81 pg/ml) and patients aged ≥70 (46.92±6.77 pg/ml) in comparison with male controls (29.96±3.30 pg/ml, p=0.026) and controls aged ≥70 (23.62±4.43 pg/ml, p=0.009). In comparison to similar controls, Cohen's d effect size for patients aged ≥70 years was found to be 0.90. The findings reveal a higher serum level of IL-37 in patients with TCC, which might be clinically associated with immunosuppression and tumor growth. However, this is a preliminary study, and more research on the biological role of IL-37 and its potential therapeutic effects in bladder cancer is required.

Immunological Estimation of Inflammatory Interleukins (IL-4, IL-6 &amp; IL-10) Among Patients with Bladder Cancer

The aim of this study was to determine Immunomolecular expression of inflammatory interleukins (IL-4, IL-6 &amp; IL-10) by using ELISA, conventional PCR and Sequencing technologies, to give acknowledge about the roles of these interleukins in patients with bladder cancer in Basrah province. A case-control study included 85 confirmed bladder cancer patients and 80 individual as a control group. Data about age, gender, smoking, alcohol drinking, family history, occupation, residency and clinical findings for all patients with urothelial carcinoma were collected. This study show the effect of demographical factors ( age, gender smoking, family history, alcohol drinking, occupation and residency) in patients with bladder cancer. The current study measure interleukins (IL-4, IL-6 &amp; IL-10) concentration (pg\ml) by using ELISA technology among various age groups, gender, tumor sages (T1-T4) and case status (newly diagnosed, advance &amp; recurrence). The results show significant increase of interleukins 4, 6 and 10 in comparison with control group (P-value= 0.008, 0.009, 0.001) respectively.

IL-1 Signaling Promotes Clonal Expansion and Progression of Bone Marrow Fibrosis in JAK2V617F-Induced Myeloproliferative Neoplasm

Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell derived myeloid malignancies characterized by aberrant production of myeloid, erythroid or megakaryocytic lineage cells. JAK2V617F is the most common somatic driver mutation associated with MPN. Interestingly, JAK2V617F mutation can also be detected in healthy individuals with clonal hematopoiesis of indeterminate potential (CHIP) who do not exhibit overt changes in blood counts. This suggests that other factors might be involved in association with JAK2 mutation in clonal expansion and initiation/progression of MPN. Chronic inflammation is frequently associated with MPN. Interleukin 1 (IL-1) is a major regulator of inflammation. IL-1 consists of two related cytokines IL-1α and IL-1β. Both IL-1α and IL-1β bind to the IL-1 receptor 1 (IL-1R1) to initiate downstream signaling. Although elevated expression of IL-1α and IL-1β has been observed in MPN, their role in the pathogenesis of MPN has remained elusive.In this study, we investigated the role of IL-1 signaling in JAK2V617F-induced MPN using a Jak2V617F knock-in mouse model. We observed elevated levels of IL-1α and IL-1β in mice expressing heterozygous (Jak2 VF/+) and homozygous Jak2V617F (Jak2 VF/VF) compared with WT control animals. Notably, IL-1α and IL-1β expression was significantly higher in Jak2 VF/VF mice exhibiting extensive bone marrow (BM) fibrosis compared with Jak2 VF/+ mice exhibiting polycythemia vera (PV), consistent with elevated levels of IL-1 in patients with myelofibrosis (MF).Since both IL-1α and IL-1β levels were elevated in Jak2 VF/VF mice exhibiting MF, we utilized conditional IL-1R1 knockout (IL-1R1cKO) and Jak2 VF/VF mice to assess the role of IL-1 signaling in the initiation/progression of MF. As expected, Jak2 VF/VF mice exhibited a significant increase in WBC, neutrophil and platelet counts compared to WT control mice. Deletion of IL-1R1in Jak2 VF/VF mice (IL-1R1cKO; Jak2 VF/VF) significantly reduced the WBC, neutrophil and platelet counts to almost control levels. Flow cytometric analysis also showed a significant reduction of myeloid (Gr-1 +) and megakaryocytic (CD41 +) precursors in the BM and spleens of IL-1R1cKO; Jak2 VF/VF mice compared to Jak2 VF/VF mice. Moreover, deletion of IL-1R1 significantly reduced hematopoietic stem and progenitor cells (HSPC) in the BM of IL-1R1cKO; Jak2 VF/VF mice compared to Jak2 VF/VF mice. Spleen weight was significantly reduced in IL-1R1cKO; Jak2 VF/VF mice compared with Jak2 VF/VF mice and they were comparable to control WT mice. More importantly, deletion of IL-1R1 markedly reduced BM fibrosis in Jak2 VF/VF mice. These data suggest an important role of IL-1 signaling in the progression of BM fibrosis in Jak2V617F-induced MPN.To test whether IL-1 signaling contributes to clonal expansion of JAK2 mutant HSPC, we performed competitive transplantation assays by mixing Mx1Cre; Jak2 VF/+ and Mx1Cre; IL-1R1 F/F; Jak2 VF/+ mice BM cells with CD45.1 + WT mice BM cells at a ratio of 1:1 and transplanted into lethally irradiated CD45.1 + recipient animals. At 4 weeks after BMT, the recipient animals were injected with pI-pC to induce Jak2V617F expression and IL-1R1 deletion. We observed significantly higher percentages of total CD45.2 + cells as well as CD45.2 + myeloid (Gr-1 +), B- and T-cells in the peripheral blood of chimeric mice receiving Jak2 VF/+ BM compared with chimeric mice receiving IL-1R1cKO; Jak2 VF/+ BM. We also observed significantly reduced percentages of CD45.2 + LSK, LK, Gr-1 + and CD41 + cells in the BM of chimeric recipient animals receiving IL-1R1cKO; Jak2 VF/+ BM compared with Jak2 VF/+ BM. These results suggest a role of IL-1 signaling in clonal expansion of Jak2V617F mutant HSPC.Additionally, we tested the effects of blocking IL-1R1 using an anti-IL-1R1 antibody in the homozygous Jak2V617F knock-in mouse model of MF. We observed that anti-IL-1R1 antibody treatment significantly reduced peripheral blood WBC and neutrophil counts and decreased HSPC and myeloid precursors in the BM of Jak2 VF/VF mice. Furthermore, anti-IL-1R1 antibody treatment significantly reduced splenomegaly and markedly reduced BM fibrosis in Jak2 VF/VF mice, suggesting that therapies targeting IL-1R1 could be useful for the treatment of myelofibrosis. Overall, our results suggest that IL-1 signaling contributes to clonal expansion of Jak2V617F mutant HSPC and progression of bone marrow fibrosis in MPN. DisclosuresNo relevant conflicts of interest to declare.

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin-10 in Patients with Acute Pancreatitis.

BackgroundAcute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity.Material/MethodsEnrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients.ResultsIn our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769–0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542–0.715]), our predictive model (AUC 0.918 [95% CIs 0.875–0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05).ConclusionsThe predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

Galectin-3 and Interleukin-17: A potential role in the pathogenesis of human papilloma virus infection.

In many cases, human papillomavirus (HPV) infection is self-limiting, as innate and adaptive cell-mediated immunity is needed for infection elimination; however, the inability of the immune system in some patients to clear the infection is a matter of debate. The interleukin-17 (IL-17) family cytokines play an important protective role in host immune response to infections, through maintaining immunity against specific pathogens, induction of antimicrobial proteins, and recruitment of neutrophils to sites of invasion. Galectin-3 (Gal-3) may be considered as a marker of viral infection as many studies reported its increased serum level in viral infections. To evaluate levels of serum Gal-3 and IL-17 in patients with verrucas and to explore the potential role of these markers in the pathogenesis of the disease. Fifty patients suffering from HPV Infection, and fifty healthy controls were included in this study. Serum levels of Gal-3 and IL-17 were assessed using enzyme-linked immunosorbent assay. The patients' serum Gal-3 was significantly higher, while IL-17 was significantly lower than that of the healthy controls (p-value<0.001). Moreover, a statistically significant positive correlation was found between Gal-3 serum level and disease duration and number of warts. Significant negative correlation exists between IL-17 and Gal-3 levels. Our results indicate a potential role of both IL-17 and Gal-3 in the pathogenesis of warts and open a new opportunity in targeting these markers in the future in treating warts.