Interleukin-6 Response Research Articles

Immunophenotypes of anti-SARS-CoV-2 responses associated with fatal COVID-19.

BackgroundThe relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood.MethodsLongitudinal prospective cohort of hospitalized patients with COVID-19 (N=254) was followed up to 35 d after admission (median, 8 d). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T, B, NK lymphocyte subsets and serum interleukin-6 response. We used machine learning to identify patterns of the immune response, and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors.ResultsOverall, 45 (18%) patients died within 28 days after hospitalization. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod, and the anti-S1-IgGhighTlowBmodNKmodIL-6highest had a high risk of fatal COVID-19 (HR, 3.36–21.69; 95% CI, 1.51–163.61 and HR, 8.39–10.79; 95% CI, 1.20–82.67; P≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6mod and anti-S1-IgGlowThighestBhighestNKhighestIL-6low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1- anti-S1-IgGhighThighBmodNKmodIL-6low and anti-S1-IgGhighestThighestBhighNKhighIL-6lowest clusters were characterized by a very low risk of mortality.ConclusionsBy employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6 mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.

Divergent splanchnic sympathetic efferent nerve pathways regulate interleukin-10 and tumour necrosis factor-α responses to endotoxaemia.

The efferent branches of the splanchnic sympathetic nerves that enhance interleukin-10 (IL-10) and suppress tumour necrosis factor-α (TNF) levels in the reflex response to systemic immune challenge were investigated in anaesthetized, ventilated rats. Plasma levels of TNF and IL-10 were measured 90min after intravenous lipopolysaccharide (LPS, 60µg/kg). Splanchnic nerve section, ganglionic blockade with pentolinium tartrate or β2 adrenoreceptor antagonism with ICI 118551 all blocked IL-10 responses. Restoring plasma adrenaline after splanchnic denervation rescued IL-10 responses. TNF responses were disinhibited by splanchnic denervation or pentolinium treatment, but not by ICI 118551. Splanchnic nerve branches were cut individually or in combination in vagotomized rats, ruling out any vagal influence on results. Distal splanchnic denervation, sparing the adrenal nerves, disinhibited TNF but did not reduce IL-10 responses. Selective adrenal denervation depressed IL-10 but did not disinhibit TNF responses. Selective denervation of either spleen or liver did not affect IL-10 or TNF responses, but combined splenic and adrenal denervation did so. Finally, combined section of the cervical and lumbar sympathetic nerves did not affect cytokine responses to LPS. Together, these results show that the endogenous anti-inflammatory reflex is mediated by sympathetic efferent fibres that run in the splanchnic, but not other sympathetic nerves, nor the vagus. Within the splanchnic nerves, divergent pathways control these two cytokine responses: neurally driven adrenaline, acting via β2 adrenoreceptors, regulates IL-10, while TNF is restrained by sympathetic nerves to abdominal organs including the spleen, where non-β2 adrenoreceptor mechanisms are dominant. KEY POINTS: An endogenous neural reflex, mediated by the splanchnic, but not other sympathetic nerves, moderates the cytokine response to systemic inflammatory challenge. This reflex suppresses the pro-inflammatory cytokine tumour necrosis factor-α (TNF), while enhancing levels of the anti-inflammatory cytokine interleukin-10 (IL-10). The reflex enhancement of IL-10 depends on the splanchnic nerve supply to the adrenal gland and on β2 adrenoreceptors, consistent with mediation by circulating adrenaline. After splanchnic nerve section it can be rescued by restoring circulating adrenaline. The reflex suppression of TNF depends on splanchnic nerve branches that innervate abdominal tissues including, but not restricted to, spleen: it is not blocked by adrenal denervation or β2 adrenoreceptor antagonism. Distinct sympathetic efferent pathways are thus responsible for pro- and anti-inflammatory cytokine components of the reflex regulating inflammation.

The ketone body β-hydroxybutyrate mitigates ILC2-driven airway inflammation by regulating mast cell function.

Ketone bodies are increasingly understood to have regulatory effects on immune cell function, with β-hydroxybutyrate (BHB) exerting a predominantly anti-inflammatory response. Dietary strategies to increase endogenous ketone body availability such as the ketogenic diet (KD) have recently been shown to alleviate inflammation of the respiratory tract. However, the role of BHB has not been addressed. Here, we observe that BHB suppresses group 2 innate lymphoid cell (ILC2)-mediated airway inflammation. Central to this are mast cells, which support ILC2 proliferation through interleukin-2 (IL-2). Suppression of the mast cell/IL-2 axis by BHB attenuates ILC2 proliferation and the ensuing type 2 cytokine response and immunopathology. Mechanistically, BHB directly inhibits mast cell function in part through GPR109A activation. Similar effects are achieved with either the KD or 1,3-butanediol. Our data reveal the protective role of BHB in ILC2-driven airway inflammation, which underscores the potential therapeutic value of ketone body supplementation for the management of asthma.

Anti-IL-10 Antibody Humanization by SDR Grafting with Enhanced Affinity to Neutralize the Adverse Response of Interleukin-10

Anti-IL-10 Antibody Humanization by SDR Grafting with Enhanced Affinity to Neutralize the Adverse Response of Interleukin-10

Interleukin-6, undercarboxylated osteocalcin, and brain-derived neurotrophic factor responses to single and repeated sessions of high-intensity interval exercise

ObjectivesThe purpose of this study was to compare the effects of a single session of high-intensity interval exercise (HIIE) with 2 consecutive HIIEs, separated by 3 h of recovery, on plasma interleukin-6 (IL-6), undercarboxylated osteocalcin (ucOC), and brain-derived neurotrophic factor (BDNF) responses. MethodsTwenty male recreational endurance athletes completed two HIIE trials in a randomized crossover design: a single session of HIIE on the single exercise day (HIIE-S) and two sessions of HIIE 3 h apart on the double exercise day (HIIE-D). The HIIE protocol consisted of 10 × 1 min cycling at 100 % of peak oxygen uptake, with 75 s of low-intensity cycling at 60 W. Blood samples were collected to analyze IL-6, ucOC, and BDNF levels before and immediately after HIIE on the HIIE-S and before and immediately after the second HIIE on the HIIE-D. ResultsBoth HIIE interventions significantly increased (p < 0.001) plasma IL-6 (HIIE-S 33.90 % vs HIIE-D 31.04 %; p = 0.64), ucOC (HIIE-S 37.18 % vs HIIE-D 39.54 %; p = 0.85), and BDNF levels (HIIE-S 236.01 % vs HIIE-D 216.68 %; p = 0.69), with no group effect. ConclusionsOur results demonstrate that performing two consecutive HIIEs on the same day with a 3-h rest results in similar changes in plasma levels of IL-6, BDNF, and ucOC compared with a single session of HIIE.

Cellular and Humoral Immunity against Different SARS-CoV-2 Variants Is Detectable but Reduced in Vaccinated Kidney Transplant Patients.

In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta, and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARS-CoV-2-specific IFN-γ responses after booster vaccination than healthy controls. However, SARS-CoV-2-specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha, and delta, and 7.8-fold higher for omicron (p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients displayed antibodies to variants of SARS-CoV-2. Thus, KTX patients should be partly protected, due to neutralizing antibodies to variants of SARS-CoV-2 or by cross-reactive T cells, especially those producing IL-2.

Child Maltreatment and Inflammatory Response to Mental Stress Among Adults Who Have Survived a Myocardial Infarction.

Experiences of child maltreatment are associated with cardiovascular risk and disease in adulthood; however, the mechanisms underlying these associations are poorly understood. We examined associations between retrospectively self-reported exposure to child maltreatment (Early Trauma Inventory Self-Report Short Form) and inflammatory responses to mental stress among adults (mean age = 50 years) who recently had a myocardial infarction ( n = 227). Inflammation was assessed as blood interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), and monocyte chemoattractant protein-1 concentrations, measured before and after a standardized public speaking stress task. We used mixed linear regression models adjusting for cardiovascular disease severity, medication usage, and psychosocial, demographic, and life-style factors. In women, increases in IL-6 levels and MMP-9 levels with stress were smaller in those exposed to sexual abuse, relative to those unexposed (IL-6 geometric mean increases = 1.6 [95% confidence interval {CI} = 1.4-1.9] pg/ml versus 2.1 [95% CI = 1.8-2.4] pg/ml; MMP-9 geometric mean increases = 1.0 [95% CI = 0.9-1.2] ng/ml versus 1.2 [95% CI = 1.1-1.4] ng/ml). No differences were noted for emotional or physical abuse. By contrast in men, individuals exposed to sexual abuse had larger IL-6 responses than those not exposed to abuse. These findings suggest sex differences in stress response among survivors of a myocardial infarction exposed to abuse early in life. They also underscore the importance of examining sex as an effect modifier of relationships between exposure to early life adversity and inflammatory responses to mental stressors in midlife.

The Correlation Between Toll-Like Receptor-5 Gene Polymorphism with Serum Level of Toll–Like Receptor-5 and Interleukin-6 and Interleukin-12 Response to Toxoplasma Gondii in Pregnant Women

Background: Toxoplasma gondii is an obligate intracellular parasite that can cause variable clinical symptoms or can even be asymptomatic in immunocompetent individuals. The parasite is known to cause congenital diseases, ocular, and miscarriage in pregnant women. Primary infections are dangerous in pregnant women, that occurring usually asymptomatically, especially in the first trimester. Different rates of pregnant women are infected with Toxoplasma gondii in different countries. Primary infections in pregnant women result in transmission of Toxoplasma. gondii through the placenta to the fetus and then in congenital infections, and it is not the only reason for miscarriage, the activity of Toll -like receptors in defense against Toxoplasma gondii infections was observed such as Toll-like receptor5 molecule, and some cytokines (such as IL-6, and IL-12 ), maybe lead to abortion. Several single-nucleotide polymorphisms (SNPs) residing in genes encoding these receptors were reported as significant genetic modifications of Toll- like receptors and correlated with miscarriage. Objectives : Study the correlation of TLR-5 gene polymorphism in pregnant women infected with toxoplasmosis, and study association of TLR-5 polymorphisms with the serum level of TLR-5 and cytokines (IL-6, IL-12) in pregnant women infected with toxoplasmosis. Methods: The present Case-control study was conducted on 100 women, of which fifty pregnant women seropositive (IgG, IgM) for Toxoplasma gondii (Group1), fifty pregnant women seronegative (IgG, IgM) for Toxoplasma gondii (Group2), as a control group, collected in the period from January 2021 to December 2021.

Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial

Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (β = − 0.274, p = .03) and feelings of social disconnection (β = − 0.307, p = .01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p = .02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression.Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012.

Porcine reproductive and respiratory syndrome virus reinfection causes the distribution of porcine interleukin-4 in close proximity to B lymphocytes within lymphoid follicles and a reduction in B and T lymphocytes

Interleukin 4 (IL-4) plays a major role in T-lymphocyte development and is thought to be a central regulator as a cofactor in resting B-lymphocyte proliferation. Primary infection with porcine reproductive and respiratory syndrome virus (PRRSV) induces minimal IL-4 production, whereas an IL-4 response occurs in the peripheral blood of piglets reinfected by PRRSV. The locations and interaction partners for the massive volume of IL-4 triggered by PRRSV reinfection remain unclear. This study aimed to investigate the characteristics of IL-4 secretion and location changes in peripheral immune organs induced by PRRSV infection and reinfection. Our results show that PRRSV reinfection induced higher levels of IL-4 mRNA and protein expression in the peripheral immune organs (e.g., lymph node and spleen) and peripheral blood compared with PRRSV primary infection. Importantly, we found that, following PRRSV reinfection, an obvious large-scale migration of IL-4 occurred in the lymph nodes. During PRRSV primary infection, IL-4 was mainly concentrated around the lymphoid follicles and paracortical regions of the lymph node and also located in the marginal area and periarterial lymphatic sheath region of the spleen. During PRRSV reinfection, the now abundant IL-4 gathered into the lymphoid follicles of the lymph node and spleen. Notably, IL-4 changed its location state from scattered and sparse during primary infection to clinging to B lymphocytes in the lymphoid follicles during reinfection. During reinfection, IL-4 was often co-localized with T and B lymphocytes; furthermore, the percentages of several T lymphocyte subsets, N protein-specific antibody levels, and viral load in the peripheral blood or lymph tissues underwent remarkable variation. Another important finding of this study was that the numbers of B lymphocytes and T lymphocytes in the lymphoid nodes were significantly reduced after PRRSV infection or reinfection, presumably due to PRRSV-induced acute bone marrow failure and autophagy in thymic epithelial cells. This study revealed the characteristics of IL-4 migration and distribution in the peripheral lymph organs induced by PRRSV reinfection and provides valuable clues for further exploration of the interactions between IL-4, B lymphocytes, and T lymphocytes during PRRSV infection and reinfection.

Cellular and Humoral Immunity after the Third Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplant Recipients.

Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell transplantation (HSCT). We analyzed immune responses before and after a third vaccination in HSCT patients and healthy controls. Cellular immunity was assessed using interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpots. Furthermore, this is the first report on neutralizing antibodies against 11 variants of SARS-CoV-2, analyzed by competitive fluorescence assay. Humoral immunity was also measured by neutralization tests assessing cytopathic effects and by ELISA. Neither HSCT patients nor healthy controls displayed significantly higher SARS-CoV-2-specific IFN-γ or IL-2 responses after the third vaccination. However, after the third vaccination, cellular responses were 2.6-fold higher for IFN-γ and 3.2-fold higher for IL-2 in healthy subjects compared with HSCT patients. After the third vaccination, neutralizing antibodies were significantly higher (p < 0.01) in healthy controls, but not in HSCT patients. Healthy controls vs. HSCT patients had 1.5-fold higher concentrations of neutralizing antibodies against variants and 1.2-fold higher antibody concentrations against wildtype. However, half of the HSCT patients exhibited neutralizing antibodies to variants of SARS-CoV-2, which increased only slightly after a third vaccination.

Caffeine Augments the Lactate and Interleukin‐6 Response to Moderate‐Intensity Exercise in Men But Not Women

The release of interleukin 6 (IL‐6) from contracting skeletal muscle is thought to contribute to some of the health benefits bestowed by exercise. This IL‐6 response appears proportional to exercise volume. Unfortunately, high volumes of exercise are not feasible for all people. Caffeine augments the magnitude of increase in circulating concentration of IL‐6 in response to high‐intensity and long‐duration exercise, in men. Caffeine is also known to increase circulating concentrations of lactate during exercise. One of the mechanisms thought to contribute to IL‐6 release from exercising skeletal muscle is lactate production. We hypothesized that caffeine, ingested prior to moderate‐intensity exercise, would lead to greater circulating concentrations of lactate and IL‐6 in a study population comprising both men and women. 15 healthy adults (9 males and 6 females, aged 26±7 years, (mean ± SD)) completed 30‐minutes of moderate‐intensity cycle ergometer exercise, equivalent to the ventilatory threshold, after ingesting either caffeine (6 mg/kg) or placebo. Arterialized‐venous blood was collected throughout each of the exercise sessions. Compared with placebo, caffeine increased end‐exercise circulating concentrations of lactate (5.72±3.95 vs. 7.14±4.66 mmol/L, P&lt;0.001) but not end‐exercise IL‐6 (1.84±0.97 vs. 2.37±1.04 pg/mL, P=0.139). However, when women were excluded from the analysis, caffeine augmented (P=0.04) the magnitude of increase of end‐exercise IL‐6 concentration (1.80±0.86 vs. 2.57±1.21 pg/mL); this effect was further exaggerated after 30‐minutes of inactive recovery (3.81±2.32 vs. 5.06±3.22 pg/mL). Noteworthy, caffeine evoked greater end‐exercise lactate concentrations in data sets containing only men (P=0.02) and only women (P=0.002) but did not influence the IL‐6 response in women (P=0.94). Our preliminary data imply that in men unable/unwilling to perform high‐intensity and/or long duration exercise, caffeine may potentially enhance the IL‐6 mediated health benefits of relatively short, moderate intensity exercise.

Sequential Submaximal Training in Elite Male Rowers Does Not Result in Amplified Increases in Interleukin-6 or Hepcidin.

Previous research investigating single bouts of exercise have identified baseline iron status and circulating concentrations of interleukin-6 (IL-6) as contributors to the magnitude of postexercise hepcidin increase. The current study examined the effects of repeated training bouts in close succession on IL-6 and hepcidin responses. In a randomized, crossover design, 16 elite male rowers completed two trials, a week apart, with either high (1,000mg) or low (<50mg) calcium pre-exercise meals. Each trial involved two, submaximal 90-min rowing ergometer sessions, 2.5hr apart, with venous blood sampled at baseline; pre-exercise; and 0, 1, 2, and 3hr after each session. Peak elevations in IL-6 (approximately 7.5-fold, p < .0001) and hepcidin (approximately threefold, p < .0001) concentrations relative to baseline were seen at 2 and 3hr after the first session, respectively. Following the second session, concentrations of both IL-6 and hepcidin remained elevated above baseline, exhibiting a plateau rather than an additive increase (2hr post first session vs. 2hr post second session, p = 1.00). Pre-exercise calcium resulted in a slightly greater elevation in hepcidin across all time points compared with control (p = .0005); however, no effect on IL-6 was evident (p = .27). Performing multiple submaximal training sessions in close succession with adequate nutritional support does not result in an amplified increase in IL-6 or hepcidin concentrations following the second session in male elite rowers. Although effects of calcium intake require further investigation, athletes should continue to prioritize iron consumption around morning exercise prior to exercise-induced hepcidin elevations to maximize absorption.

Periosteum-induced ossification effect in skull defect through interleukin-8 and NF-κB pathway: An experimental study with Oryctolagus cuniculus rabbits.

Background: The purpose of this study was to analyze the response of inflammatory cytokines interleukin-8 (IL-8) and NF-κB to the closure of skull defect with periosteum as a scaffolding material in bone healing used after surgery.Methods: Thirty Oryctolagus cuniculus rabbits underwent a craniotomy to create a 20 mm diameter round defect in the parietal bones. The parietal bones were returned to its place and stabilized by an internal plate fixation. The defects were either left empty or implanted with periosteum. At 6 weeks, the specimens were euthanized and examined.Results: Histological examination showed a more well-developed formation of woven bone in the periosteum group. Immunohistochemical examinations showed that the use of periosteum in the closure of skull defects reduced the NF-κB and IL-8 response which affected the ossification process.Conclusion: The experiment showed that the use of periosteum was linked with IL-8 and NF-κB downregulation toward ossification effects at any point throughout the trial. Periosteum usage might be beneficial as a scaffolding material in bone healing for autograft cranioplasty in animal model and could be applied to clinical practice.

Genetic deletion of IL-6 increases CK-MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise.

The intensity, duration, type of contraction, and muscle damage influence interleukin-6 (IL-6) response to acute exercise. However, in response to an exhaustive exercise session, the upregulation of IL-6 in the serum and heart is associated with an inflammatory condition and can inhibit autophagy. This study aimed to investigate the role of IL-6 in autophagy pathway responses and mitochondrial function in the heart of mice submitted to acute exhaustive physical exercise. The mice were allocated into three groups, five animals per group, for the wild type (WT) and the IL-6 knockout (IL-6 KO): Basal (sedentary; Basal), 1 h (after 1 h of the acute exercise; 1 h), and 3 h (after 3 h of the acute exercise; 3 h). After the specific time for each group, the blood was collected, each mouse heart was removed, and the left ventricle (LV) was isolated. In summary, under basal conditions, without the influence of the acute exercise, the IL-6 KO group showed lower number of nuclei in the cardiac tissue, but higher collagen deposition; lower messenger RNA(mRNA) levels of Prkaa1 and Mtco1, but higher mRNA levels of Ulk1; and higher protein levels of the ratio p-AMPK/AMPK in the heart when compared to WT at the same time point. After the acute exercise (1and 3 h), the IL-6 KO group had lower mRNA levels of Tfam, Mtnd1, Mtco1, and Nampt in the heart when compared to WT after exercise; higher serum levels of creatine kinase(CK), CK-MB, and lactate dehydrogenase for the IL-6 group when compared to the WT group after the exercise. Specifically, the heat-shock protein 60protein levels in the heart increased 3 h after exhaustive exercise in the WT group, but not in the IL-6 KO group. The study emphasizes that IL-6 may offer cardioprotective effects, including mitochondrial adaptations in response to acute exhaustive exercise.

Effects of air pollution exposure on inflammatory and endurance performance in recreationally trained cyclists adapted to traffic-related air pollution.

The aim of the present study was to analyze the effects of traffic-related air pollution (TRAP) on markers of inflammatory, neuroplasticity, and endurance performance-related parameters in recreationally trained cyclists who were adapted to TRAP during a 50-km cycling time trial (50-km cycling TT). Ten male cyclists performed a 50-km cycling TT inside an environmental chamber located in downtown Sao Paulo (Brazil), under TRAP or filtered air conditions. Blood samples were obtained before and after the 50-km cycling TT to measure markers of inflammatory [interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1)] and neuroplasticity [brain-derived neurotrophic factor (BDNF)]. Rating of perceived exertion (RPE), heart rate (HR), and power output (PO) were measured throughout the 50-km cycling TT. There were no significant differences between experimental conditions for responses of IL-6, CRP, and IL-10 (P > 0.05). When compared with exercise-induced changes in filtered air condition, TRAP provoked greater exercise-induced increase in BDNF levels (TRAP = 3.3 ± 2.4-fold change; Filtered = 1.3 ± 0.5-fold change; P = 0.04) and lower exercise-induced increase in ICAM-1 (Filtered = 1.1 ± 0.1-fold change; TRAP = 1.0 ± 0.1-fold change; P = 0.01). The endurance performance-related parameters (RPE, HR, PO, and time to complete the 50-km cycling TT) were not different between TRAP and filtered air conditions (P > 0.05). These findings suggest that the potential negative impacts of exposure to pollution on inflammatory, neuroplasticity, and performance-related parameters do not occur in recreationally trained cyclists who are adapted to TRAP.

Influence of a proinflammatory state on postprandial outcomes in elderly subjects with a risk phenotype for cardiometabolic diseases

PurposeLow-grade inflammation in obesity is associated with insulin resistance and other metabolic disturbances. In response to high-energy meal intake, blood concentrations of inflammatory markers, glucose and insulin rise. The aim of this study was to examine whether a basal inflammatory state influences postprandial responses.MethodsA randomized crossover trial was performed in 60 participants with a cardiometabolic risk phenotype (age 70 ± 5 years; BMI 30.9 ± 3.1 kg/m2). Each participant consumed three different iso-energetic meals (4300 kJ): a Western diet-like high-fat meal (WDHF), a Western diet-like high-carbohydrate meal (WDHC) and a Mediterranean diet-like meal (MED). Blood samples were collected when fasted and hourly for 5 h postprandially and analyzed for glucose, insulin, interleukin-1β (IL-1β), interleukin-6 (IL-6) and endothelial adhesion molecules. Based on fasting serum C-reactive protein (CRP) concentrations, participants were assigned to a high inflammation (CRP ≥ 2.0 mg/L; n = 30) or low inflammation (CRP < 2.0 mg/L; n = 30) group, and postprandial outcomes were compared.ResultsPlasma IL-6, glucose and serum insulin increased after all meals, while IL-1β and endothelial adhesion molecules were unchanged. The high inflammation group had higher fasting and postprandial IL-6 concentrations than the low inflammation group, although the IL-6 response slope was similar between groups. In response to the WDHC meal, participants in the high inflammation group experienced a higher glycaemic response than those in the low inflammation group.ConclusionA basal proinflammatory state results in higher absolute fasting and postprandial IL-6 concentrations, but the increase in IL-6 relative to basal levels is not different between high and low inflammation groups. Elevated glycaemic response in the high inflammation group may be due to inflammation-induced short-term insulin resistance.The trial was registered at http://www.germanctr.de and http://www.drks.de under identifier DRKS00009861 (registration date, January 22, 2016).

Keel bone damage affects behavioral and physiological responses related to stress and fear in two strains of laying hens.

Keel bone damage (KBD) is more prevalent in alternative laying hen housing systems than in conventional cages, and its incidence differs from strain to strain. However, the information of KBD in Lindian chickens, a native Chinese strain, is limited. To investigate the effect of KBD on fearfulness and physiological indicators of stress in Lindian chickens and commercial laying hens, a total of two hundred 25-wk-old chickens (100 Hy-line Brown and 100 Lindian chickens) were studied for 7wk. The birds were housed in furnished cages with 10 birds per cage for each strain. At 32-wk of age, the birds in each strain were divided into normal (NK), deviated (DK), and fractured (FK) hens according to the keel bone status. Ten birds in each keel bone status per strain were subsequently selected to collect blood for the determination of stress and fear-related indicators, including corticosterone, serotonin, interleukin-1β, and interleukin-6, and measure fear responses, including novel object test (NOT), human approach test (HAT), and tonic immobility (TI) test. The results showed that egg production was lower and the incidence of keel bone fractures was higher in Lindian chickens than in Hy-line Brown hens (P < 0.05). Lindian chickens showed a significantly increased whole blood serotonin content, NOT-latency, HAT-score, and TI induction times (P < 0.05) and decreased serum interleukin-6 content and TI-duration (P < 0.05) compared with Hy-line Brown hens. Additionally, FK hens had significantly elevated whole blood corticosterone, serum interleukin-1β and interleukin-6 levels, TI-duration, and NOT-latency (P < 0.05), and a reduced whole blood serotonin content (P < 0.05) compared with NK and DK hens. Our results indicated that KBD affected stress and fear responses, and this impact was mainly reflected by FK hens compared with NK and DK hens. We suggest that keel bone fractures are the main factor impairing hen welfare. Besides, the incidence of keel bone fractures and stress and fear responses of Lindian chickens are more severe than Hy-line Brown laying hens, indicating that the strain type can affect the health and welfare of laying hens.

Abstract P084: Sex Differences In Testosterone On Interleukin-6 At Baseline And In Response To Mental Stress

Introduction: Young and middle-aged women with ischemic heart disease are a high-risk group for morbidity and mortality particularly after a myocardial infarction (MI). This group exhibits higher concentrations of the inflammatory cytokine interleukin-6 (IL-6) at baseline and in response to mental stress compared to men. The reasons for these differences are unknown; however, sex hormones may play a role. While testosterone has been shown to have anti-inflammatory effects among men; the role of testosterone on inflammatory cytokines among women has been understudied, and no research has examined the influence of testosterone on IL-6 response to stress. Hypothesis: Among young and middle-aged patients with a recent MI, higher concentrations of testosterone have anti-inflammatory effects among men at baseline and in response to mental stress; but are associated with greater inflammation among women. Methods: We studied 269 patients 61 years old or younger who were hospitalized for a MI in the previous 8 months. We measured plasma IL-6 (pg/mL) before and 90 minutes after mental stress (speech task). Inflammatory response was defined as the difference between IL-6 levels 90-minutes post mental stress and resting values. Serum free testosterone (pg/mL) was measured before mental stress. Differences across sex and time were examined with mixed models for repeated measures after natural log-transformation of IL-6. Results: The mean age was 51 years (range: 26-61); 48% were women and 64% African American. Mean values of free testosterone among men and women were 12.6 pg/mL (range: 0.9-29.0) and 1.8 pg/mL (range: 0.3-15.6), respectively. After adjusting for demographic factors (age, race, income), lifestyle and medical history (BMI, hypertension, diabetes, depression) and medication use, the association of testosterone with the IL-6 response to stress differed by sex (p for testosterone-by-sex-by-time interaction = 0.06). Among men, higher levels of testosterone were associated with lower concentrations of IL-6 at rest (β = -0.04; p = &lt;.0001), but was attenuated after stress (β = -0.001; p = 0.93). This change in slopes across time or inflammatory response for men was significant (p = &lt;.0001). In contrast, among women, higher levels of testosterone tended to be associated with higher IL-6 at rest (β = 0.04; p = 0.07) and after stress (β = 0.04; p = 0.14), indicating no change between time points or inflammatory response to stress (p=0.75). Conclusions: Among young and middle-aged survivors of a recent MI, higher concentrations of free testosterone are associated with lower inflammation among men, but with an opposite trend of higher inflammation among women.

A surgical study of serological markers such as C-reactive protein and interleukin 6 in response to postoperative infection in patients with open fractures in a tertiary care hospital

&lt;p&gt;To study the response of C-reactive protein (CRP) and interleukin-6 (IL-6) to postoperative infection in patients with open fractures.&lt;strong&gt; &lt;/strong&gt;Thirty patients with open fractures of extremities within 12 hours of injury were included in study. Blood samples were collected for Postoperative infection is a devastating complication of open fractures. The ideal investigation for early diagnosis of infection should be done before surgery and should be accurate, convenient to patient, cause minimal morbidity. Test such as CRP and IL-6 estimation is utilized in this study. CRP and IL 6 estimation on admission, second and fourth post-op day. All patients underwent surgery and reports evaluated. It was observed that CRP peak on post-op day 4 and IL 6 on postoperative day 2 in patients with infection before clinical evidence of infection. This prospective study includes 30 cases, followed up in ward for a week. Various factors regarding clinical presentation, findings of various investigations, operative treatment had been analyzed. The sensitivity of CRP in our study was 100%, and specificity was 42%. The persistent rise of CRP value seen within the infected group was statistically significant (p&amp;lt;0.05). The present clinical study of estimation of CRP and IL 6 to detect postoperative infection in patients after open fractures is an excellent diagnostic test for early detection and management of infection.&lt;/p&gt;