Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action.

Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30 ± 3 years; body mass index: 22.8 ± 2.3 kg/m2; V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ : 51 ± 6 mL/kg/min) completed a no-exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30 min after and 90 min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti-inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis (P < 0.001) and increased plasma IL-6 (P < 0.001), IL-10 (P = 0.0145) and tumour necrosis factor-⍺ (TNF-⍺) (P = 0.0338) concentrations in an intensity-dependent manner (HCE and/or HIE vs. CTL). These systemic changes coincided with a diminished ability of IL-10/6 to phosphorylate STAT3 (P < 0.001) and inhibit TNF-⍺ secretion (P = 0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE (P = 0.0933) and HIE (P = 0.0187) vs. CTL] and a tendency for higher CD163 expression (HCE vs. CTL, P = 0.0985), suggesting that hyporesponsiveness to anti-inflammatory cytokine action does not impede the ability of exercise to promote an anti-inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise. KEY POINTS: Circulating cytokine concentrations are frequently used to evaluate the anti-inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti-inflammatory cytokine action - measured using a combination of intracellular signalling and cytokine secretion ex vivo - in distinct immune cell subpopulations after acute calorie-matched exercise bouts differing in intensity and pattern. Anti-inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise.

Potential tools for predicting response to chemotherapy in OC: Assessment of immune dysbiosis, participant's self-rated health and microbial dynamics.

Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance mechanisms contribute to poor OC 5-year survival rates. Peripheral inflammation is linked to various disease states and we previously identified unique peritoneal microbial features predictive of OC. We hypothesized that unique peripheral immune profiles and peritoneal microbial features may be predictive of disease-free interval (time to recurrence) and response to chemotherapy in participants with OC. We also investigated self-rated health (SRH) scores in the context of peripheral inflammation as a potential screening tool for OC. Blood and peritoneal fluid were collected from participants with OC or a benign adnexal mass (BPM). Lymphocyte populations were analyzed using Fluorescence Activated Cell Sorting, serum cytokine levels were analyzed using the Human Th17 Magnetic Bead Panel assay and peritoneal fluid microbial features were analyzed using Next Generation Sequencing (NGS). Participants completed a standardized questionnaire on self-rated physical and emotional health. Participants were classified into three chemotherapy response categories: platinum-refractory, platinum-resistant or platinum-sensitive. A significant positive correlation was found between elevated inflammatory status on the day of surgery and longer disease-free interval. SRH measures did not correlate with immune status in participants with OC or a BPM. We identified a correlation between peritoneal microbial features and chemotherapy response. We conclude that immune dysbiosis may be useful in predicting OC recurrence. The immune findings reported here set the framework for additional studies utilizing immune profiles to predict platinum-based chemotherapy responsiveness in OC.

Assessment of progranulin and FAM19A5 protein blood levels in patients with metabolic syndrome.

Progranulin and family with sequence similarity 19, member A5 (FAM19A5) protein are adipokines with growing importance in the context of metabolic diseases. The study aimed to determine the serum concentration of progranulin and FAM19A5 in people with metabolic syndrome (MS) compared to those without MS. The concentration of progranulin and FAM19A5 was determined in 45 people with MS (group A) and in 35 healthy people without MS (group B). Body composition analysis, blood pressure, blood oxygen saturation and anthropometric measurements were performed. There were no differences in the blood levels of progranulin and FAM19A5 between the groups. In group A, the level of progranulin was 29.25±36.92 pg/ml and in group B it was 46.00±60.12pg/ml (p=0.2693). The level of FAM19A5 was 163.16±55.11 pg/ml and 197.57±112.89 pg/ml (p=0.1341) in subjects with and without metabolic syndrome, respectively. In group A, there was a correlation between FAM19A5 and diastolic blood pressure (DBP) (R= -0.40) and high-density lipoprotein (HDL) level (R= -0.37). In group B, correlations were found between progranulin and waist circumference (R= -0.43) and progranulin and triglyceride (TG) levels (R= -0.42). Both groups together showed correlations between progranulin level and body mass index (R= -0.24), HDL (R=0.25) and TG levels (R= -0.25) and between FAM19A5 level and DBP (R= -0.34). In conclusion, patients with and without MS do not differ in the range of progranulin and FAM19A5 serum levels. In patients with MS, elevated FAM19A5 serum levels may be an indicator of dyslipidaemia development. FAM19A5 appears to be a better predictor of MS than progranulin.

Assessment of the Diagnostic Utility of Serum Omentin 1 and IL-6 in Early Stages of Diabetic Nephropathy.

In India, diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Timely detection of microalbuminuria and appropriate intervention can reverse or arrest the progress of nephropathy. The pathogenesis of diabetic nephropathy has revealed that during the early onset of kidney involvement in diabetics, inflammation and fibrosis progress from tubular to glomerular damage. This study was designed to elucidate the association of chemokines, Omentin 1, and interleukin 6 (IL-6) with microalbuminuria. MATERIAL: Settings and Design: This cross-sectional observational study was conducted as a collaborated study in the Departments of General Medicine and Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, India, during 2019-2020. METHODS AND MATERIAL: Our study group comprised 116 diabetes mellitus patients. They were grouped into two, each of 58 on the basis of their urine albumin levels; Group 1 (controls) had UACR < 30 µg/mg, eGFR> 90ml/ min and Group 2 (cases) had UACR ≥ 30 µg/mg and < 300 µg/mg, eGFR>60ml/min and < 90ml/min. Serum omentin 1 and IL-6, creatinine, glycated haemoglobin (HbA1c), fasting (FBS) and postprandial blood sugar (PPBS), lipid profile, total protein, albumin, and fasting insulin, HOMA-IR were studied. OBSERVATION: Our study showed that Omentin 1 levels were decreased, and IL-6 levels were increased in the DN group compared to the T2DM without DN. The risk estimates calculated revealed that diabetes mellitus patients having an IL-6: omentin ratio ≥ 0.26 had Odds of 3.97 of developing DN, which was statistically significant (CI 2.36-6.68). Therefore, a ratio of ≤ 0.26 was found to be kidney protective among diabetes mellitus patients. CONCLUSION: From the results of this present study, we recommend that estimation of serum IL-6: omentin 1 ratio of T2DM will aid in identifying early stages of DN before the onset of microalbuminuria.

Clinical and immunological allergy assessment in cancer patients.

Cancer is associated with immunodeficiency, while allergies result from immune system hyperactivity mediated by cytokines and immunoglobulins. The purpose of this study was to determine the relationship between immune environment of specific cancers and allergies, emphasizing cytokines related to Th1 and Th2 responses associated with IgE. 80 adults were distributed into two groups: control (n = 20) and cancer (n = 60), distributed in three subgroups (n = 20), head and neck, stomach, and prostate cancers. This study compared Th1 (IL-2) and Th2 (IL-4) parameters, anti-inflammatory, pro-inflammatory, or regulatory profile regarding both IgE levels and reported allergies, by means of clinical manifestations and IgE, IL-1ß, IL-2, IL-4, IL-17, and TGF-ß serum concentration. Clinically allergies were observed in 50% of the control group and in 20% of the cancer group (p = 0.009). IL-2 cytokine and TGF-ß concentrations were higher in the patients with cancer as compared to the control (p < 0.005). However, there were IL-4, IL-17, and IL-1ß decreases in the patients with cancer (p < 0.05). No correlation was observed between the cytokines studied and IgE and clinically proven allergies in both investigated groups. There was an inverse association between cancer and clinical allergy manifestations. In head and neck, stomach, and prostate cancers, an immunosuppressive serum tumor environment was predominant. There was no difference in cytokines related to Th1 and Th2 parameters in relation to IgE. No correlation was found between clinically proved allergies and immunity markers related to the same allergens.

Altered Cytokine Response of Human Brain Endothelial Cells after Stimulation with Malaria Patient Plasma.

Infections with the deadliest malaria parasite, Plasmodium falciparum, are accompanied by a strong immunological response of the human host. To date, more than 30 cytokines have been detected in elevated levels in plasma of malaria patients compared to healthy controls. Endothelial cells (ECs) are a potential source of these cytokines, but so far it is not known if their cytokine secretion depends on the direct contact of the P. falciparum-infected erythrocytes (IEs) with ECs in terms of cytoadhesion. Culturing ECs with plasma from malaria patients (27 returning travellers) resulted in significantly increased secretion of IL-11, CXCL5, CXCL8, CXCL10, vascular endothelial growth factor (VEGF) and angiopoietin-like protein 4 (ANGPTL4) if compared to matching controls (22 healthy individuals). The accompanying transcriptome study of the ECs identified 43 genes that were significantly increased in expression (≥1.7 fold) after co-incubation with malaria patient plasma, including cxcl5 and angptl4. Further bioinformatic analyses revealed that biological processes such as cell migration, cell proliferation and tube development were particularly affected in these ECs. It can thus be postulated that not only the cytoadhesion of IEs, but also molecules in the plasma of malaria patients exerts an influence on ECs, and that not only the immunological response but also other processes, such as angiogenesis, are altered.

Social Stressors, Arboviral Infection, and Immune Dysregulation in the Coastal Lowland Region of Ecuador: A Mixed Methods Approach in Ecological Perspective.

Aedes aegypti, the mosquito that transmits arboviral diseases such as dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV), is present in tropical and subtropical regions of the world. Individuals at risk of mosquito-borne disease (MBD) in the urban tropics face daily challenges linked to their socio-environment conditions, such as poor infrastructure, poverty, crowding, and limited access to adequate healthcare. These daily demands induce chronic stress events and dysregulated immune responses. We sought to investigate the role of socio-ecologic risk factors in distress symptoms and their impact on biological responses to MBD in Machala, Ecuador. Between 2017 and 2019, individuals (≥ 18 years) with suspected arbovirus illness (DENV, ZIKV, and CHIKV) from sentinel clinics were enrolled (index cases, N = 28). Cluster investigations of the index case households and people from four houses within a 200-m radius of index home (associate cases, N = 144) were conducted (total N = 172). Hair samples were collected to measure hair cortisol concentration (HCC) as a stress biomarker. Blood samples were collected to measure serum cytokines concentrations of IL-10, IL-8, TNF-α, and TGF-ß. Univariate analyses were used to determine the association of socio-health metrics related to perceived stress scores (PSS), HCC, and immune responses. We found that housing conditions influence PSS and HCC levels in individuals at risk of MBD. Inflammatory cytokine distribution was associated with the restorative phase of immune responses in individuals with low-moderate HCC. These data suggest that cortisol may dampen pro-inflammatory responses and influence activation of the restorative phase of immune responses to arboviral infections.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

BACKGROUND: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. AIMS: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. METHODS: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. RESULTS: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. DISCUSSION: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

Assessment of clinical variables as predictive markers in the development and progression of colorectal cancer.

Colorectal cancer (CRC) is graded as one of the most common cancer. It accounts for the second leading cause of cancer deaths worldwide. The present study intends to investigate the role and importance of different biochemical variables in the development of colorectal cancer.In this cross-sectional study we recruited ninety-one patients diagnosed with colorectal cancer and fifty-three age-sex matched controls from June 2017 to June 2018. Different variables i.e. SOD, GSH, CAT, MDA, TGF, VEGF, TNF, ILs, MMPs, etc., were estimated with the help of their respective methods. Our findings suggest a significant increase in the levels of different inflammatory and stress-related markers. The NFκB, TGF-ß, VEGFß, 8OHdG, IsoP-2α were significantly found to be increased in patients with colon cancer (0.945 ± 0.067 µg/ml, 18.59 ± 1.53 pg/ml, 99.35 ± 4.29 pg/ml, 21.26 ± 1.29 pg/ml, 102.25 ± 4.25 pg/ml) as compared to controls (0.124 ± 0.024 µg/ml, 8.26 ± 0.88 pg/ml, 49.58 ± 2.62 pg/ml, 0.93 ± 0.29 pg/ml, 19.65 ± 3.19 pg/ml). Notably, the levels of different antioxidants were shown to be significantly lower in patients of colon cancer. The present study concluded that excessive oxidative stress and lipid peroxidation result in a decrease in the antioxidative capacity of cells which may influence diverse signaling cascades including NF-KB, which results in DNA modification and gene transcription that ultimately involved in the progression of colon cancer.

Assessment of cellular and molecular changes in the rat brain after gamma radiation and radioprotection by anisomycin.

The objective of the study was to describe cellular and molecular markers of radioprotection by anisomycin, focusing on the changes in rat brain tissue. Two-month-old Wistar rats were exposed to a 60Co radiation source at a dose of 6 Gy, with or without radioprotection with anisomycin (150 mg/kg) administered subcutaneously 30 min before or 3 or 6 h after irradiation. Survivors were analyzed 30 days after treatment. Astroglial and microglial responses were investigated based on the expression of glial markers assessed with immunohistochemistry, and quantitative changes in brain biomolecules were investigated by Raman microspectroscopy. In addition, blood plasma levels of pro-inflammatory (interleukin 6 and tumor necrosis factor α) and anti-inflammatory (interleukin 10) cytokines were assessed. We found that application of anisomycin either before or after irradiation significantly decreased the expression of the microglial marker Iba-1. We also found an increased intensity of Raman spectral bands related to nucleic acids, as well as an increased level of cytokines when anisomycin was applied after irradiation. This suggests that the radioprotective effects of anisomycin are by decreasing Iba-1 expression and stabilizing genetic material by increasing the level of nucleic acids.

Extracorporeal Cytokine Adsorption Therapy As a Preventive Measure in Cardiac Surgery and As a Therapeutic Add-On Treatment in Sepsis: An Updated Systematic Review of Comparative Efficacy and Safety.

OBJECTIVES: Evaluating whether there is a clinical benefit of using extracorporeal cytokine adsorption therapy in two indications. DESIGN: Systematic review. SETTING: Search on four databases, Medline, Embase, The Cochrane Library, and the European Network for Health Technology Assessment planned and ongoing projects database. PATIENTS: Patients with sepsis/septic shock; patients undergoing cardiac surgery. INTERVENTIONS: Cytokine adsorption. MEASUREMENTS AND MAIN RESULTS: Randomized controlled trials and prospective studies with concurrent control were eligible for the evidence synthesis. The quality of the individual studies and the strength of the available evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach, respectively. For the preventive treatment of extracorporeal cytokine adsorption therapy in patients undergoing cardiac surgery, we found very low-quality inconclusive evidence for mortality (five randomized controlled trials, n = 163), length of stay in the ICU (five randomized controlled trials, n = 163), and length of hospitalization (three randomized controlled trials, n = 101). Very low-quality inconclusive evidence was found for (serious) adverse events (four randomized controlled trials, n = 148). For the therapeutic treatment of extracorporeal cytokine adsorption therapy in patients with sepsis/septic shock, we found very low-quality inconclusive evidence for mortality up to 60-day follow-up (two randomized controlled trials, n = 117), organ function (two randomized controlled trials, n = 117) and length of stay in the ICU (one randomized controlled trial, n = 20). Very low-quality inconclusive evidence was found for (serious) adverse events (two randomized controlled trials, n = 117). CONCLUSIONS: Given the available evidence, the efficacy and safety of extracorporeal cytokine adsorption therapy in combination with standard care in the investigated indications was not established. We strongly recommend considering well-powered studies with patient-relevant endpoints instead of investing further research funds on studies that may not shed light on the clinical benefit of extracorporeal cytokine adsorption therapy.

Performance of a commercially available multiplex platform in the assessment of circulating cytokines and chemokines in patients with rheumatoid arthritis and osteoarthritis.

BACKGROUND/OBJECTIVE: Cytokines and chemokines (cytokines) are central to rheumatoid arthritis (RA) pathogenesis, with increasing use of multiplex immunoassays in clinical/research settings. Rheumatoid factor (RF) may interfere with assay outcomes by nonspecifically binding detection analytes. We evaluated the performance of a commercially available multiplex platform, including assessment of the impact of RF depletion. METHODS: Forty-five cytokines were tested using Meso Scale Discovery V-PLEX™ and samples from 40 RA and 40 osteoarthritis (OA) patients. Select samples were depleted of RF using a commercial binder. Performance was assessed using intra-assay coefficients of variation (CV), intraclass correlation coefficients (ICC), percent change following RF depletion, and disease discrimination. Values above or below quantification thresholds were imputed. RESULTS: Of the 45 cytokines analyzed, 31 yielded CVs <10%; none demonstrated CVs >30%. ICCs universally exceeded 0.85 with the exception of eight analytes. RF depletion altered cytokine values by <15% for 40 analytes with larger changes (>30%) only seen for one analyte. Twenty-three cytokines differed significantly based on measurement in plasma vs. serum. Three analytes were higher in the serum of RA vs. OA (IL-10, IP-10, TNFα), and none were significantly greater in OA vs. RA. Seventeen analytes required imputation for >50% of the samples tested, primarily related to concentrations below the lower limit of quantification threshold. CONCLUSION: The results from this commercially available multiplex assay were generally highly reproducible and interference induced by RF only meaningfully impacted the quantification of five of the analytes examined.

Subepithelial autoimmune bullous dermatoses disease activity assessment and therapy.

Subepidermal (subepithelial) autoimmune blistering dermatoses are a group of rare skin disorders characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The fourth article in this continuing medical education series presents the current validated disease activity scoring systems, serologic parameters, treatments, and clinical trials for bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus, anti-p200 pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.

Assessment of a 4-Week Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal Symptoms and Inflammatory Parameters among Patients with Irritable Bowel Syndrome.

Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, 'abdominal pain', 'bloating/flatulence' and 'intestinal symptoms´ influence on daily life' scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ -50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.

Clinical disease activity and flare in SLE: Current concepts and novel biomarkers.

Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs primarily in females of childbearing age, with increased prevalence and severity in minority populations. Despite improvements in treatment modalities, SLE patients frequently experience periods of heightened disease activity and flare that can lead to permanent organ damage, increased morbidity, and early mortality. Such outcomes impair quality of life and inflict a significant socioeconomic burden. Predicting changes in SLE disease activity could allow for closer monitoring and preemptive treatment, but existing clinical, demographic and serologic markers have been only modestly predictive. Novel, proactive approaches to clinical disease management are thus critically needed. Panels of blood biomarkers can detect a breadth of immune pathway dysregulation that captures SLE heterogeneity and disease activity. Alterations in the balance of pro-inflammatory and regulatory soluble mediators have been associated with changes in clinical disease activity and are detectable several weeks prior to clinical flare occurrence. A soluble mediator score has been highly predictive of impending flare in both European American and African American SLE patients, and this score does not require a priori knowledge of specific pathway activation in the patient. We review current concepts of disease activity and flare in SLE, focusing on the potential of novel blood biomarkers to characterize and predict changes in disease activity. Measuring the disordered immune response in SLE in this way promises to improve disease management and prevent organ damage in SLE.

Assessment of synovial fluid and serum cytokine levels in children with septic arthritis.

Acute septic arthritis (ASA) is a common orthopedic infection of children which may produce devastating sequelae and chronic morbidity. Improved understanding of the intra-articular inflammatory response in ASA may identify cytokine targets with diagnostic or therapeutic potential, though no detailed investigations to this end have been performed. Given this, we used a multiplex cytokine assay for assessment of levels of 40 different cytokines in the synovial fluid and blood of children with ASA. Twelve children (8 controls undergoing orthopedic surgery for non-infectious conditions and 4 with ASA) were prospectively enrolled. Blood and synovial fluid were collected intraoperatively from each subject, and the levels of 40 cytokines were determined using a multiplex assay. Cytokines were organized by function and structure into 12 groups for analysis. The Benjamini-Hochberg method was used to control for type 1 errors, with an a priori false discovery rate of 10%. Subjects with ASA were younger than controls (mean age 8.0 vs 13.1 years, p=0.0400). Significant elevations were seen in interleukins (IL) with chemokine properties, IL-6 and those in the common-γ chain group in the blood and synovial fluid of children with ASA compared with controls, while significant elevations in 5 additional cytokine groups were seen in synovial fluid from children with ASA compared with controls, most notably IL-6 (median 8294.3 vs 10.7 pg/mL, p=0.0066). Our pilot study is the first to describe in detail the cytokine response in children with ASA, and highlights the need for additional study.

Similarities and differences between HIV and SARS-CoV-2.

In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.

High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4 h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P < 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P < 0.05). AA women had higher postprandial IL-1ß protein concentration and IL-8 gene expression compared with CA women (P < 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1ß, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.

Assessment of hepatic functions, hematopoietic cytokines and haematological parameters in people occupationally exposed to volatile petroleum hydrocarbons.

Humans are occupationally exposed to volatile petroleum hydrocarbons through inhalation and ingestion. To access the effect of exposure to volatile hydrocarbons, hematopoietic cytokines, haematological parameters and hepatic functions were assayed for in 100 subjects. Male participants showed significant increase (p < 0.05) in erythropoietin, interleukin-3, alanine transaminase (ALT), alkaline phosphatase (ALP), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV) and significant decrease (p < 0.05) in mean cell hemoglobin (MCH). Female participants showed significant increase (p < 0.05) in interleukin-3, ALT, AST, ALP, MCHC, MCV and significant decrease (p < 0.05) in MCH, platelets, hemoglobin and hematocrit compared to their controls. Exposure to volatile petroleum hydrocarbons raised the absolute red blood cell indices and liver enzymes and could stimulate combined increase in the release of erythropoietin and interleukin-3 leading to ineffective hematopoiesis.

Relationship between inflammation and metabolic regulation of energy expenditure by GLP-1 in critically ill children.

BACKGROUND & AIMS: Critical illness is associated with derangement in the metabolic and inflammatory response. Previous investigators have highlighted the cross-link between feeding, inflammation and gut homeostasis. Glucagon like peptide-1 (GLP-1) is a gut derived hormone that plays an important role in the modulation of energy metabolism through appetite regulation and promotion of gastric motility. Growing evidence suggests that GLP-1 might influence energy expenditure. The aim of this study was to assess the relationship between inflammatory activation and metabolic regulation of energy expenditure by assessing cytokine release, levels of GLP-1 and energy expenditure in a cohort of critically ill children. METHOD: This is a prospective study conducted in critically ill children. A blood sample was collected from each child during the first few days of critical illness, for the analysis of serum inflammatory cytokines (TNF-α, IL-10, IL-6 and IL-1ß) and GLP-1 in 42 children. Indirect calorimetry (IC) measurements were performed concurrently in a subset of 21 children. The metabolic index was determined using the ratio of Measured Resting Energy Expenditure (MREE)/Predicted Resting Energy Expenditure (PREE) based on the Schofield equation. Correlation analysis was performed, followed by a stepwise linear regression analysis to assess factors affecting GLP-1 and the metabolic index. RESULTS: A total of 42 children (0-14 years) were included in this study. The regression analysis indicated that CRP, TNF-α, IL-6 and IL-1ß statistically influenced GLP-1 concentrations (p < 0.01). Where IC measurements were performed (N = 21), GLP-1 showed a statistically significant association with the metabolic index (p < 0.01). No evidence of statistical association was recorded between the inflammatory mediators and the metabolic index. Overall the results showed that circulating GLP-1 was increased in response to inflammatory stimuli in critically ill children. GLP-1 contributed to the changes observed in MREE induced by critical illness in our cohort. CONCLUSION: Energy expenditure is extremely variable in critically ill children, our study suggests that changes in GLP-1 might contribute to a significant amount of this variation. If confirmed in larger studies, GLP-1 could be used as a correction factor for REE predictive equations in critically ill children.