Higher Serum Levels Of IL-6 Research Articles

Factors impacting Catecholamines in Caregivers of Patients with Dementia

Background: Caregivers of dementia patients have significantly higher levels of serum IL-6 and CRP compared to non-caregivers, and the accumulation of everyday stressors reportedly promotes the induction of inflammatory markers. However, few studies have identified factors that affect catecholamine levels in caregivers who experience a combination of physical and mental stress from caregiving.Purpose: This study aimed to identify physical factors that impact catecholamine levels in caregivers of dementia patients.Methods: Participants were elderly caregivers living together with elderly Alzheimer’s-type dementia patients. We performed logistic regression analysis, with levels of adrenaline, noradrenaline, and dopamine (indicators of catecholamine) as dependent variables.Results: Caregiver BMI had a significant impact on adrenaline levels (OR: 0.792; 95%CI: 0.654-0.960) and noradrenaline levels (OR: 1.210; 95%CI: 1.009-1.451), whereas age had a significant impact on dopamine levels (OR: 1.162; 95%CI: 1.019-1.324).Discussion: While caregiver BMI significantly impacted adrenaline and noradrenaline levels, the mechanism underlying these relationships is unclear. One possibility is that obesity (BMI) and a rise in sympathetic nerve activity contributed to hypertension. Our findings suggest that chronic stress in elderly caregivers may potentially impair the dopaminergic activation system in the brain.Conclusion: There is a need to identify factors which increase BMI in caregivers. Future studies aimed at gaining a better understanding of the lifestyle habits of caregivers and intervention studies aimed at reducing their BMI are warranted.

IL-6 and IL-10 are associated with disease severity and higher comorbidity in adults with COVID-19

AimCOVID-19 pandemic has caused extensive burden on public life and health care worldwide. This study aimed to assess circulating levels of inflammatory cytokines in adult patients who were hospitalized with COVID-19 and stratified according to age (older or younger than 65 years) aiming to explore associations between these markers of inflammation and comorbidities. MethodsThis was a cross-sectional study of 142 COVID-19 patients consecutively admitted to the University Hospital of the Federal University of São Carlos, from July to October 2020. Sociodemographic data, chronic comorbidities, and baseline NEWS2 and SOFA for clinical deterioration were obtained at hospital admission. Serum levels of inflammatory cytokines were determined by flow cytometry. ResultsOlder adults with COVID-19 had higher serum levels of IL-6 and IL-10 as compared to those under 65 years of age (p < 0.001 and p = 0.003, respectively). IL-10 was independently associated with age (p = 0.04) and severity of the disease (p = 0.05), whereas serum levels of IL-6 were not directly associated with age (p = 0.5). The comorbidity index seems to be the main responsible for this, being significantly associated with IL-6 levels among those aged 65 and over (p = 0.007), in addition to the severity of the disease. ConclusionsHigher serum levels of IL-6 and IL-10 are associated with the severity of the disease and a higher comorbidity index among adults aged 65 and over with COVID-19. This should raise awareness of the importance of comorbidity index, rather than age, during risk stratification.

Association and Interaction Between Serum Interleukin-6 Levels and Metabolic Dysfunction-Associated Fatty Liver Disease in Patients With Severe Coronavirus Disease 2019.

Background and AimCirculating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19.MethodsA total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD.ResultsPatients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3–20.0] vs. 4.8 [2.6–11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05–1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008).ConclusionsPatients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.

Investigation of TNF-α and IL-6 Levels in the Sera of Non-Melanoma Skin Cancer Patients.

Background:TNF-α and IL-6 are both pleiotropic cytokines playing major roles in cancer-associated cytokine networks. They have previously been investigated for their function in skin malignancies, mostly melanomas, and studies on NMSC patients are relatively rare. In this study, we aimed to assess the associations of serum levels of IL-6 and TNF-α with NMSCs and its clinicopathological features. Methods:This cases-control study was carried out to investigate the serum levels of TNF-α and IL-6 in 70 NMSC patients, in comparison with 30 healthy individuals, by means of flow cytometric bead-based immuneoassay. Results:Serum levels of both TNF-α and IL-6 were significantly higher in NMSC patients (6.470 vs. 4.355 pg/ml; p = 0.0468, respectively), compared to healthy individuals (3.205 vs. 0.000 pg/ml; p = 0.0126, respectively). In the subgroup analysis, SCC patients had higher serum levels of IL-6 compared to healthy individuals (3.445 vs. 0.000 pg/ml; p = 0.0432). No other significant differences were observed in the serum levels of these two cytokines among different clinicopathological subgroups of the patients. Conclusion:The increased levels of TNF-α and IL-6 in NMSC patients can be introduced as an epiphenomenon of a complex cancer-induced cytokine cascade.

P0731 / #2140: SARS-COV-2-RELATED MULTISYSTEM INFLAMMATORY SYNDROME IN FAMILIAL REFRACTORY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A CASE REPORT

AIMS & OBJECTIVES: To describe how the clinical course of children positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tested with reversetranscriptase polymerase chain reaction (RT-PCR) has changed lately from non-severe to life threatening cases. METHODS: Case report. A 2-month-old baby arrived at the emergency department for fever, anemia, leukopenia and thrombocytopenia, he was hospitalized and diagnosed with severe dengue. A week later, he started with respiratory symptoms and fever, he was positive for SARS-CoV-2 based on RT-PCR. Two weeks later, persistent fever, C-Reactive protein and D-dimer elevation, lymphocytopenia, anemia and thrombocytopenia integrated diagnosis of multisystem inflammatory syndrome (MIS-C) treated with intravenous immune globulin, systemic glucocorticoid and anticoagulation therapy in the intensive care unit. Nevertheless, he had persistent fever, hepatosplenomegaly, pancytopenia, hypertriglyceridemia and high serum IL-6 levels;bone marrow aspiration revealed an hemophagocytic lymphohistiocytosis (HLH), so treatment with steroid, cyclosporine and cytarabine was administrated. Antibiotic therapy was added because of clinical symptoms for septic shock. Multiple transfusions because of refractory anemia and thrombocytopenia, vasopressor management and mechanical ventilation were needed. However, because of his insidious clinical course and history of infection with SARS-CoV-2, management with inhibitor of JAK signalling was added. Physical examination revealed silver hair, suggestive for a familial HLH secondary to Griscelli syndrome type 2. RESULTS: In the end, multiple organ dysfunction (cardiovascular, hematologic, respiratory, renal, neurologic). CONCLUSIONS: MIS-C was secondary to an immunemediated injury triggered by viral infections with an overall mortality greater than 50% in previously healthy children, however additional HLH resulted in fatal outcome.

L-glutamine supplementation improves the inflammatory profile of exercised obese elderly

OBJECTIVE: To elucidate the effect of oral L-glutamine (Gln) supplementation, associated or not with the regular practice of combined-exercise training (CET), on glycemic and lipid profile and systemic inflammatory status in elderly subjects. METHODS: 84 elderly subjects, non-practitioners (NP, n=31) and practitioners of CET (n=53), were supplemented with Gln [0.3g/kg of weight plus 10g of maltodextrin, groups: NP-Gln (n=14), and CET-Gln (n=26)], or placebo [10g of maltodextrin, groups: NP-PL (n=17), and CET-PL (n=27)]. Anthropometric and physical data were assessed. Blood sampling was collected pre and post-30 days of supplementation. RESULTS: NP subgroups showed higher BMI and serum IL-6 levels than CET subgroups before and post-supplementation. Higher serum levels of IL-10 with lower IL-6 and IL-6/IL-10 ratio were observed post-supplementation in the CET-Gln subgroup than pre-supplementation. When the volunteers were separated according to their BMI, higher IL-6 levels were found in all obese (OB) subgroups than in the adequate weight (AW) subgroups before supplementation. This difference was not maintained between OB CET-Gln and AW CET-Gln subgroups post-supplementation. Higher levels of IL-10 with lower IL-6 and IL-6/IL-10 ratio were found in the OB CET-Gln subgroup post-supplementation than pre-supplementation. No differences were found in the glycemic and lipid profile. CONCLUSION: Oral Gln supplementation when associated with the regular practice of CET can modulate the systemic inflammatory status, especially in obese elderly subjects.

Electrocardiographic modifications and cardiac involvement in COVID-19 patients: results from an Italian cohort.

The aim of this study was to detect predisposing CV risks factors and ECGs changes in COVID-19 patients. The study population included 60 noncritically ill patients with COVID-19 pneumonia admitted to our hospital between 16 March and 11 May 2020. Electrographic changes, evaluated from ECGs acquired at admission and at 7 days after starting COVID-19 therapy, were analysed. We also compared 45 patients without CV involvement with 15 patients with new onset of cardiac adverse events during hospitalization. ECGs under treatment showed a lower heart rate (HR) (69.45 ± 8.06 vs 80.1 ± 25.1 beats/min, P = 0,001) and a longer QRS (102.46 ± 15.08 vs 96.75 ± 17.14, P = 0.000) and QT corrected (QTc) interval (452.15 ± 37.55 vs 419.9 ± 33.41, P = 0,000) duration than ECGs before therapy. Fifteen patients (25%) showed clinical CV involvement. Within this group, female sex, lower ejection fraction (EF), low serum haemoglobin, high Troponin I levels (TnI), low lymphocytes count, high serum IL-6 levels, or use of Tocilizumab (TCZ) were more represented. Patients admitted for SARS-CoV2 infection and treated with anti-COVID-19 drug therapy develop ECG changes such as reduction in HR and increase in QRS duration and QTc interval. One in four patients developed CV events. Gender, EF, heamoglobin values, TnI, lymphocytes count, IL-6 and use of TCZ can be considered as predisposing factors for CV involvement.

Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden

OBJECTIVES:Fabry disease (FD) is an X-linked lysosomal disease caused by variants of the GLA gene; the formation of defective alpha-galactosidase A contributes to the accumulation of substrates in several organs. Chronic inflammation is thought to contribute to organ damage in FD patients.METHODS:In total, 36 classic FD patients (15 men/21 women) and 25 healthy controls (20 men/8 women) were assessed. The Mainz Severity Score Index (MSSI) was established after conducting interviews with the patients and chart review. Serum IL-6, IL-1β, and TNF-α levels were evaluated in both groups.RESULTS:The mean age (years) for FD patients was 43.1±15.4 and that for the controls was 47.4±12.2 (p>0.05). Twenty-two patients (59.5%) were treated with enzyme replacement therapy (ERT). Serum IL-6 and TNF-α levels were significantly higher in FD patients than in the controls. Patients treated with ERT had higher serum IL-6 and TNF-α levels than those not treated with ERT. There was no difference in the serum IL-1β levels between patients treated with ERT and those who were not. The MSSI scores in the patients were correlated with serum levels of IL-6 (r=0.60, p<0.001) and TNF-α (r=0.45, p<0.001).CONCLUSION:FD was associated with elevated serum levels of IL-6 and TNF-α in this cohort. The FD patients treated with ERT, particularly, women, exhibited higher levels of serum IL-6 and TNF-α than those not treated with ERT; the serum IL-6 and TNF-α levels were correlated with the MSSI scores reflecting greater disease burden.

Characteristics of psychiatric manifestations among hospitalized COVID-19 patients and their correlation with disease severity - a cross sectional study.

COVID-19 severity, characteristics of psychiatric symptoms using a brief psychiatric rating scale, and sociodemographic variables were explored and evaluated. An exploratory study was conducted during the COVID-19 pandemic, from July 13th to July 26th 2020, in an isolation facility at the COVID-designated Sola hospital in Ahmedabad, India. A total of 201 inpatients diagnosed with COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) were included in this study. We assessed the presence and severity of psychiatric symptoms using the Brief Psychiatric Rating Scale (BPRS). Of the 201 COVID-19 patients, 63 (31.3%), 36 (18%), 16 (8%) and 14 (7%) experienced anxiety, tension, somatic concern and depressed mood respectively. The effect of the severity of COVID-19 on the mean of the total BPRS score was statistically signi- ficant (F = 17.2, p = 0.000). In the severe COVID-19 group, the mean of the total BPRS score (22.6 ± 4.8) was significantly higher than in the moderate (20.3 ± 4.0) and mild (19.1 ± 2.2) COVID-19 groups. High levels of serum ferritin, IL-6 and D-dimer were associated with the presence of neuropsychiatric symptoms like hallucinatory behavior and disorientation. The majority of COVID-19 patients experienced anxiety, tension and somatic concern. The presence of serious psy- chiatric symptoms like hallucinatory behavior and disorientation were predominantly seen in severe COVID-19 patients with signi- ficantly high serum inflammation and coagulation markers.

Evaluation of inflammatory and cardiac-electrophysiological markers in patients undergoing peritoneal dialysis.

Background: The Tp-e/QT (peak to end of T-wave duration/QT interval) ratio is a promising marker of myocardial repolarization and ventricular arrhythmogenesis. Its elevation is associated with sudden cardiac deathin different clinical conditions. This study was designed to assess the possible association between increased Tp-e/QT ratio and clinical factors in peritoneal dialysispatients. Materials & methods: We devised a prospective cross-sectional study, which included 107 patients who were divided into groups according to their Tp-e/QT ratio. The association of an increased Tp-e/QT ratio with related factors was analyzed with multivariate logistic regression. Results: Thirty-one patients, who had an elevated Tp-e/QT ratio, showed higher values of IL-6, left ventricular end-systolic diameter, Tp-e, percentage of diabetes mellitus, coronary artery calcification, and left ventricular ejection fraction. Multivariate analysis revealed that IL-6 was an independent risk factor for a higher Tp-e/QT ratio after adjustments. Conclusion: Our study revealed that a highserum IL-6 level in peritoneal dialysis patients increased the risk of a higher Tp-e/QT ratio, which indicated a potentially hazardous interplay between inflammation and arrhythmogenesis.

Clinical characteristics and predictors of mortality associated with COVID-19 in elderly patients from a long-term care facility

Since December 2019, coronavirus disease 2019 (COVID-19) pandemic has spread from China all over the world and many COVID-19 outbreaks have been reported in long-term care facilities (LCTF). However, data on clinical characteristics and prognostic factors in such settings are scarce. We conducted a retrospective, observational cohort study to assess clinical characteristics and baseline predictors of mortality of COVID-19 patients hospitalized after an outbreak of SARS-CoV-2 infection in a LTCF. A total of 50 patients were included. Mean age was 80 years (SD, 12 years), and 24/50 (57.1%) patients were males. The overall in-hospital mortality rate was 32%. At Cox regression analysis, significant predictors of in-hospital mortality were: hypernatremia (HR 9.12), lymphocyte count < 1000 cells/µL (HR 7.45), cardiovascular diseases other than hypertension (HR 6.41), and higher levels of serum interleukin-6 (IL-6, pg/mL) (HR 1.005). Our study shows a high in-hospital mortality rate in a cohort of elderly patients with COVID-19 and hypernatremia, lymphopenia, CVD other than hypertension, and higher IL-6 serum levels were identified as independent predictors of in-hospital mortality. Given the small population size as major limitation of our study, further investigations are necessary to better understand and confirm our findings in elderly patients.

Changes in the serum levels of anti-inflammatory interleukins in patients with atopic dermatitis after a course of phototherapy

BACKGROUND: The role of immunological disorders in the development of atopic dermatitis (AD) is currently beyond doubt.&#x0D; AIMS: Changes in the serum levels of IL-4, IL-10 and IL-13 in patients with atopic dermatitis (AD) after UV therapy combined with standard drug treatment have been studied.&#x0D; MATERIALS AND METHODS: The study included 80 patients with moderate to severe AD and 80 healthy volunteers. The patients with AD received a course of 311 nm UVB phototherapy combined with standard drug therapy. Serum IL-4, IL-10 and IL-13 levels were determined through enzyme-linked immunosorbent assay (ELISA).&#x0D; RESULTS: In the studied sample, patients with AD were found to have statistically significantly higher serum levels of IL-10 and IL-13 compared with healthy volunteers of the control group. Serum IL-10 level was 18.3 pg/ml in patients with AD and 13.2 pg/ml in those of the control group; the level of IL-13 was 15.8 pg/ml and 11.5 pg/ml, respectively; after the course of 311 nm UVB, serum IL-10 and IL-13 levels in patients with AD decreased (IL-10 by 27.8% and IL-13 by 12.5%). IL-4 values did not differ significantly in patients with AD and those in the control group, being 0.06 pg/ml and 0.05 pg/ml, respectively; after the course of phototherapy, serum IL-4 levels remained unchanged and were equal to 0.05 pg/ml.&#x0D; CONCLUSION: The results obtained confirm the assumptions about the significant role of IL-10 and IL-13 in the mechanisms of AD regulation and pathogenesis and demonstrate the anti-inflammatory efficacy of phototherapy (311 nm UVB) in patients with severe and moderate AD.

Erythrocyte Acetylcholinesterase Enzyme Activity, Serum Interleukin-6 Level and Respiratory Function of Myanmar Agricultural Workers Exposed to Organophosphate Pesticides

Background and Aim: Myanmar is one of the countries in production of agricultural plant commodities. Nowadays, pesticides are commonly used to increase agricultural production and productivity. Organophosphate pesticides exposure can cause many physiological changes within the body including impaired respiratory function. Therefore, the present study aimed to find out the relationship between the erythrocyte acetylcholinesterase enzyme activity, serum interleukin-6 level and respiratory functions such as forced expiratory volume in first second (FEV1), forced vital capacity (FVC), ratio of forced expiratory volume in first second and forced vital capacity (FEV1/FVC), peak expiratory flow (PEF) and average forced expiratory flow between 25% and 75% of FVC (FEF25-75%) among agricultural workers who exposed to organophosphate pesticides and non-exposed control subjects. Methods: A community-based cross-sectional, comparative study was done in agricultural workers (n = 40) who live in A-lal-chaung village, Magway Township and age/BMI matched non-exposed subjects (n = 40) who live in Yan-Way Quarter, Magway Township. All the participants were selected according to inclusion and exclusion criteria by simple random sampling method. Erythrocyte acetylcholinesterase (AchE) enzyme activity was measured by spectrophotometric method and serum interleukin-6 levels were measured by enzymelinked immunosorbent assay (ELISA) method. Respiratory function parameters were measured by Spirobank II spirometer. Results: The mean erythrocyte acetylcholinesterase enzyme activity was significantly lower in exposed group than that of non-exposed group (3354.43±589.81 U/L vs 4515.83±759.33 U/L; p<0.001). The percentage of predicted value of respiratory function parameters of exposed group were significantly lower than that of non-exposed group (FEV1: 72.13±4.40 vs 75.95±4.05; FVC: 66.90±4.40 vs 70.60±4.20; FEV1/FVC: 110.35±2.69 vs 111.32±1.33; PEF: 5.52±8.66 vs 79.40±5.09) (p<0.05). There were significant positive correlation between erythrocyte acetylcholinesterase activity and respiratory function parameters in all groups (n=80) (FEV1: r=0.425, p<0.001; FVC: r=0.301, p<0.05 and PEF: r=0.316, p<0.05). There were significant negative correlation between erythrocyte acetylcholinesterase activity and serum IL-6 level (r= -0.374, n= 80, p<0.05). Serum IL-6 level was significantly higher in exposed group than non-exposed group (34.77±3.3 pg/mL vs 28.75±2.0 pg/mL; p <0.001). There was a significant negative correlation between serum IL-6 level and respiratory function parameters in all group (n=80) such as FEV1 (r= 0.300, p<0.05) and FVC (r= 0.331, p<0.05). Conclusion: It was concluded that agricultural workers who exposed to organophosphate pesticides have higher serum IL-6 level and lower respiratory functions than that of non-exposed subjects. The present findings highlighted that there has an impact of chronic low dose OP exposure on respiratory health and there has a role of IL-6 in respiratory function decline.

Psoriatic arthritis and depressive symptoms: does systemic inflammation play a role?

Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu. One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A. Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p < 0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p < 0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p < 0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p < 0.01). Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.

Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort.

The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.

An inflammatory cytokine signature predicts COVID-19 severity and survival.

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.

Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome.

SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a 'cytokine storm' have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with 'common cold' coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.

Effects of the IL6 -174G>C promoter polymorphism and IL-6 serum levels on the progression of cutaneous malignant melanoma.

Cutaneous malignant melanoma (CMM) is one of the most immunogenic types of cancer, with a 6-fold higher rate of spontaneous regression than any other malignancy. In addition to responsiveness to different immunotherapies, the immunogenicity of CMM highlights the important role of the host immune system in the response to CMM. The present study aimed to explore the role of two functional promoter polymorphisms [IL6 −174G>C (rs1800785) and TNFA −308G>A (rs1800629)] in the regulation of the genes encoding the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-α, specifically in patients with CMM. A total of 76 patients with CMM and 200 control subjects were genotyped using PCR-restriction fragment length polymorphism. The genotype frequencies for both single nucleotide polymorphisms (SNPs) did not differ significantly between the patients and controls (P=0.358 and P=0.810 for IL6 and TNFA, respectively). However, compared with carriers of C-allele genotypes (CG+CC), patients with the IL6 −174GG genotype exhibited more advanced melanoma (Clark scale ≥3; P=0.037) and shorter survival times, particularly those who worked outdoors (in conditions with increased sunlight exposure; P=0.016). Furthermore, the serum IL-6 levels of patients with CMM were significantly higher than those of the control subjects, which were associated with unfavorable blood and serum characteristics and tumor progression (development of new distant metastases; P=0.004), and with a shorter overall survival time (P=0.042). Using a Cox proportional hazard model, the IL6 −174GG genotype was found to be an independent prognostic factor for reduced survival time (P=0.030), together with sex (being male; P=0.004) and occupations with higher exposure to sunlight (P=0.047). In conclusion, the results of the present study indicated that the promoter polymorphisms IL6 −174G>C and TNFA −308G>A are not predisposing factors for CMM. However, the IL6 −174G>C SNP and IL-6 serum concentrations are likely to influence the progression of the disease, and the GG genotype and higher IL-6 serum levels may indicate shorter survival.

AB0775 PERIPHERAL JOINT INFLAMMATION IS ASSOCIATED WITH MORE PROATHEROGENIC CARDIOVASCULAR RISK PROFILE IN PATIENTS WITH PSORIATIC ARTHRITIS

Background:We have previously found that: (i) patients with spondyloarthritis (SpAs) have higher circulating levels of IL-18 and osteoprotegerin (OPG) than healthy controls (1), (ii) psoriatic arthritis (PsA) patients present with more proatherogenic lipid profile and higher IL-18 levels than ankylosing spondylitis (AS) patients (2)Objectives:To investigate the relationship between disease phenotype, i.e. peripheral arthritis (perPsA n=45), axial PsA (axPsA n=16) and ankylosing spondylitis (AS n=94), cardiovascular risk factors and serum concentrations of IL-18, IL-17.Methods:A group of 155 SpA patients (94 AS/61 PsA), of similar age (44.5 versus 44.9 years), disease duration (4.8 versus 6.8 years), and matched with high disease activity (AS ASDAS-CRP 3.62±0.94; PsA DAPSA 26.75±26.61) were included in the study. The lipid profile comprised triglycerides (TG), total cholesterol (tChol), low- and high-density lipoprotein (LDL and HDL, respectively) measurement. Ischemic Heart Disease (IHD) diagnosis was established from patient’s medical history. Serum concentrations of IL-17AF, IL-18 were measured by specific commercially available enzyme-linked immunosorbent assays (ELISA) and were expressed as medians (pg/ml). The Mann-Whitney test was applied for intergroup comparison, correlation was assessed using Spearman’s Rank tests (r value is shown) with linear regression model.Results:Patients with perPsA had higher rate of IHD than axPsA and AS patients (27% vs 0% vs 7.8%, respectively). perPsA patients had significantly higher diastolic blood pressure than AS patients (perPsA 131±13mmHg vs AS 121±14 mmHg), more severe cardiovascular burden than patients with axial disease, were characterised by higher occurrence of obesity (perPsA 42% vs axPsA o 18% vs 18% AS) and hypertriglyceridemia (perPsA 48% vs axPsA 14% vs 16%AS) as well as higher TG concentration (perPsA 165± 87 mg/dl vs axPsA 111± 63mg/dl vs 110± 57 AS mg/dl). Moreover, patients with perPsA had significantly higher serum concentrations of IL-18 than axPsA and AS groups (132.5pg/ml vs 79.2pg/ml vs 84.9pg/ml), but there were no differences between them in IL-17 concentrations. Interestingly, in patients with perPsA, but no other patients’ groups, statistically significant associations between IL-18 concentrations and proatherogenic risk factors were found, as IL-18 correlated positively with TC (r=0.31), TG (r=0.53) atherogenic index (r=0.6), and uric acid (r=0.3) concentrations, while negatively with HDL levels (r=-0.47). Although patients groups differ in cardiovascular risk profiles, there were no significant differences in CV risk estimation using SCORE scale (perPsA 2.3% vs 1.6% axPsA vs 2.1%AS)Conclusion:We conclude that in PsA peripheral joints inflammation is associated with more proatherogenic cardiovascular risk profile and higher IL-18 serum levels, that seem to be interrelated, while patient’s disease activity is associated with metabolic syndrome. Generally recommended SCORE scale is practically unable to indicate SpA patients with higher CV risk

Plasma IL-8 and PD-L1 and overall survival in metastatic castration-resistant prostate cancer patients (mCRPC).

e17565 Background: We previously reported the significant prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 breast cancer serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced overall survival (OS) to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). Here we correlated plasma IL-8 and PD-L1 levels with OS in mCRPC patients. Methods: 201 metastatic CRPC patients had EDTA plasma available for this retrospective analysis. Patient eligibility included chemotherapy-naive mCRPC patients. The ELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate plasma IL-8 and PD-L1. Cox regression assessed hazard ratio (HR) for OS using both categorical (median) and continuous (log-transformed) biomarkers. Results: In univariate analysis, higher plasma IL-8 levels were significantly associated with reduced OS when analyzed as a continuous variable (HR = 1.53; p = 0.003) and were of borderline significance at the median cutpoint (HR = 1.32; p = 0.069; 20.9 vs 31.5 mos median OS). Plasma PD-L1 levels were not significantly associated with OS when analyzed as a continuous variable (p = 0.17), but increased levels were significant when analyzed at the median cutpoint (HR = 1.36; p = 0.044; 21.9 vs 29.0 mos median OS). When plasma IL-8 and PD-L1 levels were combined (median cutpoints), plasma IL-8 high / PD-L1 high patients (n = 58) had a significantly shorter OS vs the plasma IL-8 low / PD-L1 low patients (n = 58) (HR = 1.69; p = 0.009; 19.3 vs 32.9 mos median OS, respectively). In multivariate analysis, when adjusted for biopsy Gleason score, age, PSA, and ECOG PS (all at time of blood draw), only high plasma IL-8 (on a continuous basis) was significantly associated with reduced OS (HR = 1.43; p = 0.019). Conclusions: In mCRPC patients, high plasma IL-8 and PD-L1 levels were associated with reduced OS (separately and combined). Circulating IL-8 and PD-L1 evaluation may inform prognosis in mCRPC and could be considered as biomarkers in future studies determining response to immune checkpoint inhibitor and anti-IL8 therapy.