Plasma Concentrations Of IL-6 Research Articles

Adalimumab Treatment Effects on Inflammation and Adipose Tissue Mitochondrial Respiration in Hidradenitis Suppurativa.

Tumour necrosis factor (TNF)-α is a proinflammatory marker and has been shown to affect mitochondrial function in different tissues. We investigated the effect on adipose tissue (AT) inflammation and mitochondrial respiration in patients with hidradenitis suppurativa (HS) after 12 weeks of treatment with adalimumab, a TNF-α inhibitor. We sampled blood and an AT biopsy from 13 patients with HS and 10 control subjects after an overnight fast. The patients were retested after at least 12 weeks of treatment with adalimumab (40 mg/week). We measured macrophage content and mitochondrial respiration in the AT and interleukin (IL)-1β, IL-6, IL-10, high-sensitivity C-reactive protein (hsCRP), interferon-γ, TNF-α, adiponectin and leptin in plasma. Clinical scores and Dermatology Quality of Life Index (DLQI) were assessed. We found a higher anti-inflammatory macrophage content (CD206+) in the patient group compared with the control group, but no differences between before and after the intervention. No difference in mitochondrial respiration was observed. We observed higher plasma IL-6 and hsCRP concentrations in patients with HS compared to controls, with no differences before and after the intervention. The difference between controls and HS patients was abolished after the intervention. HS patients improved their DLQI after the intervention with no change in clinical scores. Treatment with adalimumab in patients with HS does not alter AT inflammation or mitochondrial respiratory capacity; however, we did see a higher content of anti-inflammatory macrophages in the patient group compared with the control group.

Elevated levels of pro-thrombotic eNOS-negative platelets in COVID-19 patients

BackgroundPlatelet-rich microvascular thrombi are common in severe COVID-19. Endogenous nitric oxide (NO)-signaling limits thrombus formation and previously we identified platelet subpopulations with a differential ability to produce NO based on the presence or absence of endothelial nitric oxide synthase (eNOS). eNOS expression is counter-regulated by cytokines, and COVID-19-associated immune/inflammatory responses may affect the transcriptome profile of megakaryocytes and their platelet progeny. ObjectivesWe investigated whether the percentage of eNOS-negative to eNOS-positive platelets increases in COVID-19 patients and whether this change may be due to the actions of pro-inflammatory cytokines on megakaryocytes. MethodsPlatelets were isolated from hospitalized COVID-19 patients and COVID-19-negative controls. Platelet eNOS was measured by flow cytometry and plasma inflammatory cytokines by ELISA. Megakaryocytes from eNOS-GFP transgenic mice and the Meg-01 cell line were characterized to identify an appropriate model to study eNOS-based platelet subpopulation formation in response to inflammatory cytokines. ResultsCOVID-19 patients demonstrated a significant increase in eNOS-negative and a concomitant decrease in eNOS-positive platelets compared to controls, and this change was associated with disease severity as assessed by ICU admission. A higher eNOS-negative to –positive platelet percentage was associated with enhanced platelet activation as measured by surface CD62P. Accordingly, COVID-19 patients demonstrated higher TNF-α, IL-6, and IL-1β plasma concentrations than controls. Inflammatory cytokines associated with COVID-19 promoted eNOS-negative Meg-01 formation and enhanced subsequent eNOS-negative platelet-like particle formation. ConclusionsCOVID-19 patients have a higher percentage of eNOS-negative to –positive platelets, likely as a result of inflammatory response reducing megakaryocyte eNOS expression, which predisposes to thrombosis.

Postoperative Immunosuppression Following Breast-Conserving Surgery vs. Mastectomy: The Role of Surgical Injuries and Intraoperative Sympathetic Activation

Breast cancer is the second most prevalent cancer among all types of cancers. Objectives: To evaluate the role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conservative surgery and mastectomy. Methods: This prospective/observational study investigated 36 breast cancer patients in the Department of Surgery Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat from June 2022 to May 2023. Patients who were on schedule to undergo either mastectomy or breast-conserving surgery enrolled. Patients were categorized into two groups; Group I (breast-conserving surgery group n=18) and Group II (mastectomy group n=18). The intraoperative sympathetic activation, plasma Damage-associated molecular patterns, and postoperative immune function were compared in both groups. Descriptive statistics were done using SPSS version 28.0. Results: The overall mean age and body mass index of Group I and Group II were 62.8 ± 8.9 vs. 60.6 ± 10.6 years and 26.9 ± 3.8 vs. 25.8 ± 3.7 kg/m2, respectively. The overall duration of surgery (minutes) was 56 ± 18 and 85 ± 22, respectively. The prominent indication for surgery in Group I and Group II was Invasive carcinoma 17 (94.4%) and 11 (61.1%), respectively. The concentration of plasma alarmins and IL-6 was significantly higher in patients who underwent mastectomy as compared to breast-conserving surgery. Conclusions: It was concluded that differences in Damage-associated molecular patterns release and intraoperative sympathetic activation between mastectomy and breast-conserving surgery may influence, and potentially contribute to, postoperative immune homeostasis to improve survival seen after breast-conserving surgery.

A Pilot Study on the Effects of Exercise Training on Cardiorespiratory Performance, Quality of Life, and Immunologic Variables in Long COVID.

Objectives: Fatigue is a prominent feature of long COVID (LC) and may be related to several pathophysiologic mechanisms, including immune hyperstimulation. Aerobic endurance exercise training may be a useful therapy, with appropriate attention to preventing post-exertional malaise. Methods: Fourteen participants completed a pilot study of aerobic exercise training (twenty 1.5 h sessions of over 10 weeks). Cardiorespiratory fitness, 6 min walk distance, quality of life, symptoms, 7-day physical activity, immunophenotype, and inflammatory biomarkers were measured before and after exercise training. Results: The participant characteristics at baseline were as follows: 53.5 ± 11.6 yrs, 53% f, BMI 32.5 ± 8.4, 42% ex-smokers, 15.1 ± 8.8 months since initial COVID-19 infection, low normal pulmonary function testing, V.O2peak 19.3 ± 5.1 mL/kg/min, 87 ± 17% predicted. After exercise training, participants significantly increased their peak work rate (+16 ± 20 W, p = 0.010) and V.O2peak (+1.55 ± 2.4 mL/kg/min, p = 0.030). Patients reported improvements in fatigue severity (-11%), depression (-42%), anxiety (-29%), and dyspnea level (-46%). There were no changes in 6MW distance or physical activity. The circulating number of CD3+, CD4+, CD19+, CD14++CD16, and CD16++CD14+ monocytes and CD56+ cells (assessed with flow cytometry) increased with acute exercise (rest to peak) and was not diminished or augmented by exercise training. Plasma concentrations of TNF-α, IL-6, IL-8, IL-10, INF-γ, and INF-λ were normal at study entry and not affected by training. Conclusions: Aerobic endurance exercise training in individuals with LC delivered beneficial effects on cardiorespiratory fitness, quality of life, anxiety, depression, and fatigue without detrimental effects on immunologic function.

Obstructive sleep apnea comorbid with insomnia symptoms and objective short sleep duration is associated with clinical and preclinical cardiometabolic risk factors: Clinical implications

BackgroundInsomnia with objective short sleep duration (ISSD) but not insomnia with normal sleep duration (INSD) is associated with cardiometabolic morbidity. It has been reported that sleep apnea comorbid with insomnia (COMISA) confers higher cardiovascular risk than each condition alone. We hypothesize that the association of COMISA with clinical (hypertension) and preclinical (inflammatory and metabolic) biomarkers is driven by the ISSD phenotype. MethodsA clinical sample of 101 adults with mild-to-moderate OSA (mmOSA) (5 ≤ AHI <30) and insomnia symptoms underwent polysomnography or home sleep apnea testing, blood pressure measures (BP), fasting blood glucose, insulin, CRP and IL-6 plasma levels. Insomnia was based on PSQI. Objective short sleep duration was based on the median total sleep time of the sample. Participants were classified into 2 groups based on objective sleep duration: mmOSA with ISSD vs. mmOSA with INSD. Analysis of covariance and logistic regression analysis were conducted controlling for confounders. ResultsSystolic and diastolic BP were elevated in the ISSD group compared to INSD group (p = 0.039 and p = 0.004, respectively). Also, the risk of hypertension was significantly higher in the ISSD (OR = 3.88, 95%CI = 1.26–11.95, p < 0.05) compared to INSD group. Plasma IL-6 concentrations and insulin resistance as indexed by glucose/insulin ratio were significantly higher in the ISSD group compared to INSD group (both p < 0.05). CRP levels were not different between the two groups. ConclusionIt appears that the additive adverse effects of COMISA on cardiometabolic risks are driven by the ISSD phenotype, a finding with potential implications for further phenotyping COMISA.

Beneficial Bacteria in the Gut Microbiota May Lead to Improved Metabolic and Immunological Status in Chronic Obstructive Pulmonary Disease.

We included 16 stable COPD patients and 16 healthy volunteer CTLs. The relative abundances of Bifidobacterium spp. (Bf) and Akkermansia muciniphila (Akk) bacteria and the Bacteroidetes and Firmicutes phyla were assessed by qPCR. Pulmonary function was evaluated by spirometry, biochemical parameters by colorimetric methods and plasma cytokine levels by cytometric bead array analysis. The Firmicutes/Bacteroides ratio was related to emergency hospital visits and six-minute walk test (6MWT) results. Furthermore, the relative abundance of Bf was associated with plasma concentrations of glucose, triglycerides, HDL-C and IL-10. In addition, Firmicutes levels and the Firmicutes/Bacteroidetes ratio were associated with the IL-12/IL-10 ratio, while Akk abundance was linked to IL-12 levels. The present findings suggest that the abundance of beneficial bacteria in the GM could influence clinical presentation and immunoregulation in COPD.

Reduced plasma interleukin-6 concentration after transcranial direct current stimulation to the prefrontal cortex

ObjectivesTranscranial direct stimulation (tDCS) targeted to the dorsolateral prefrontal cortex (DLPFC) reduces food intake and hunger, but its effects on circulating factors are unclear. We assessed the effect of repeated administration of tDCS to the left DLPFC (L-DLPFC) on concentrations of pro/anti-inflammatory and appetitive hormone concentrations. Materials and methodsTwenty-nine healthy adults with obesity (12 M; 42±11 y; BMI=39±8 kg/m2) received 3 consecutive inpatient sessions of either anodal or sham tDCS targeted to the L-DLPFC during a period of ad libitum food intake. Fasting plasma concentrations of IL-6, orexin, cortisol, TNF-α, IL-1β, ghrelin, PYY, and GLP-1 were measured before the initial and after the final tDCS sessions. ResultsIL-6 (β=-0.92 pg/ml p=0.03) decreased in the anodal group compared with sham, even after adjusting for kcal intake; there were no changes in other hormones. Mean kcal intake was associated with higher IL-1β and ghrelin concentrations after the ad libitum period (β=0.00018 pg/ml/kcal, p=0.03; β=0.00011 pg/ml/kcal, p=0.02; respectively), but not differ by intervention groups. ConclusionsIL-6 concentrations were reduced following anodal tDCS to the L-DLPFC independent of ad libitum intake. IL-6 concentrations reflect the inflammatory state of adiposity and may affect eating behavior and weight gain. These findings provide evidence of therapeutic benefit of tDCS.

Mediators of monocyte chemotaxis and matrix remodeling are associated with mortality and pulmonary fibroproliferation in patients with severe COVID-19.

Acute respiratory distress syndrome (ARDS) has a fibroproliferative phase that may be followed by pulmonary fibrosis. Pulmonary fibrosis following COVID-19 pneumonia has been described at autopsy and following lung transplantation. We hypothesized that protein mediators of tissue remodeling and monocyte chemotaxis are elevated in the plasma and endotracheal aspirates of critically ill patients with COVID-19 who subsequently develop features of pulmonary fibroproliferation. We enrolled COVID-19 patients admitted to the ICU with hypoxemic respiratory failure. (n = 195). Plasma was collected within 24h of ICU admission and at 7d. In mechanically ventilated patients, endotracheal aspirates (ETA) were collected. Protein concentrations were measured by immunoassay. We tested for associations between protein concentrations and respiratory outcomes using logistic regression adjusting for age, sex, treatment with steroids, and APACHE III score. In a subset of patients who had CT scans during hospitalization (n = 75), we tested for associations between protein concentrations and radiographic features of fibroproliferation. Among the entire cohort, plasma IL-6, TNF-α, CCL2, and Amphiregulin levels were significantly associated with in-hospital mortality. In addition, higher plasma concentrations of CCL2, IL-6, TNF-α, Amphiregulin, and CXCL12 were associated with fewer ventilator-free days. We identified 20/75 patients (26%) with features of fibroproliferation. Within 24h of ICU admission, no measured plasma proteins were associated with a fibroproliferative response. However, when measured 96h-128h after admission, Amphiregulin was elevated in those that developed fibroproliferation. ETAs were not correlated with plasma measurements and did not show any association with mortality, ventilator-free days (VFDs), or fibroproliferative response. This cohort study identifies proteins of tissue remodeling and monocyte recruitment are associated with in-hospital mortality, fewer VFDs, and radiographic fibroproliferative response. Measuring changes in these proteins over time may allow for early identification of patients with severe COVID-19 at risk for fibroproliferation.

The Role of Systemic Inflammation in the Pathogenesis of Spontaneous Intracranial Hemorrhage in the Presence or Absence of Effective Cerebral Blood Flow.

Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1-3/5-8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood-brain barrier for tissue breakdown products and other neuroinflammatory factors.

Exercise4Psychosis: A randomised control trial assessing the effect of moderate-to-vigorous exercise on inflammatory biomarkers and negative symptom profiles in men with first-episode psychosis

IntroductionFirst-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. MethodsSeventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60–70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. ResultsParticipants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (−3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (–22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (−13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DiscussionRegular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.

Consumption of interesterified palm oil leads inflammation of white adipose tissue and triggers metabolic disturbances in mice on a high-fat diet

Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles.

Inhibition of phosphoinositide 3-kinase activity attenuates neutrophilic airway inflammation and inhibits pyrin domain-containing 3 inflammasome activation in an ovalbumin-lipopolysaccharide-induced asthma murine model

BackgroundExisting investigations suggest that the blockade of phosphoinositide 3-kinase (PI3K) activity contributes to inflammatory solution in allergic asthma, but whether this inhibition directly attenuates neutrophilic airway inflammation in vivo is still unclear. We explored the pharmacological effects of LY294002, a specific inhibitor of PI3K on the progression of neutrophilic airway inflammation and investigated the underlying mechanism.Methods and resultsFemale C57BL/6 mice were intranasally sensitized with ovalbumin (OVA) together with lipopolysaccharide (LPS) on days 0 and 6, and challenged with OVA on days 14–17 to establish a neutrophilic airway disease model. In the challenge phase, a subset of mice was treated intratracheally with LY294002. We found that treatment of LY294002 attenuates clinic symptoms of inflammatory mice. Histological studies showed that LY294002 significantly inhibited inflammatory cell infiltration and mucus production. The treatment also significantly inhibited OVA-LPS induced increases in inflammatory cell counts, especially neutrophil counts, and IL-17 levels in bronchoalveolar lavage fluid (BALF). LY294002 treated mice exhibited significantly increased IL-10 levels in BALF compared to the untreated mice. In addition, LY294002 reduced the plasma concentrations of IL-6 and IL-17. The anti-inflammatory effects of LY29402 were correlated with the downregulation of NLRP3 inflammasome.ConclusionsOur findings suggested that LY294002 as a potential pharmacological target for neutrophilic airway inflammation.

Age-associated declined function of endothelial progenitor cells and its correlation with plasma IL-18 or IL-23 concentrations in patients with ST-segment elevation myocardial infarction

BackgroundST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood.MethodThis study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients.ResultGRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function.ConclusionIn patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

#1502 Short-term effects of gadolinium and gadoteric acid on kidney — impact on inflammation

Abstract Background and Aims The nephrotoxicity of free gadolinium [Gd (III)] has been reported, raising concerns about the safety of gadolinium-based contrast agents (GBCA), widely used in magnetic resonance imaging. The GBCA with macrocyclic structure, such as gadoteric acid (Gd-DOTA), appear as more stable. Using human proximal tubular cells cultures, we found that free Gd (III) triggers death by apoptosis and necrosis, and increases the expression of modulators of inflammation, hypoxia and fibrosis, which are known as major risk factors for the development and worsening of kidney disease. Our aim was, using animal models, to evaluate the short-term effects of Gd (III) and of gadoteric acid on inflammatory biomarkers, at blood and renal tissue levels. Method Wistar rats were exposed to a single dose of Gd (III) or Gd-DOTA (groups A and B, respectively); a control group was also included (C). After 48h, blood and kidney samples were collected. The plasma levels of interleukin (IL)6 and transforming growth factor (TGF) beta 1 were assessed by ELISA; the kidney gene expression of IL6 (il6), TGF beta 1 (tgbf1) and nuclear factor-kappa B (nfkb1) was determined through qPCR. Results Gd (III) group (A) presented higher circulating IL6 levels (P = 0.001) and increased kidney gene expression of il6 (P = 0.013), tgbf1 (P = 0.006) and nfkb1 (P = 0.011) than the control group (C); compared to Gd-DOTA group (B), the IL6 plasma concentration (P = 0.005) and tgbf1 mRNA levels were also higher (P = 0.004). The Gd-DOTA group (B) presented increased gene expression of il6 (P = 0.006) than the control group (C). Conclusion Short-term exposition to free Gd (III) induced an inflammatory response, shown by the increase in circulating IL6, and in kidney gene expression of il6, tgbf1 and nfkb1. The exposition to Gd-DOTA was associated with a lower inflammatory response, showing only increased kidney gene expression of il6. Despite the much safer profile for Gd-DOTA, further studies are warranted, evaluating other biomarkers, to clarify the short-term, and even the long-term effects, of these compounds. Acknowledgements This work was financed by FCT through the project 2022.08400.PTDC; FCT, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.

Central angiotensin-(1–7) attenuates hypoglycemia in sepsis-like conditions via reducing systemic and hepatic inflammation

Sepsis is understood as the result of initiating systemic inflammation derived from an inadequate host response against pathogens. In its acute phase, sepsis is marked by an exacerbated reaction to infection, tissue damage, organ failure, and metabolic dysfunction. Among these, hypoglycemia, characterized by disorders of the gluconeogenesis pathway, is related to one of the leading causes of mortality in septic patients. Recent research has investigated the involvement of sympathetic efferent neuroimmune pathways during systemic inflammation. These pathways can be stimulated by several centrally administered drugs, including Angiotensin-(1–7) (Ang-(1–7)). Therefore, the present study aims to evaluate the effects of central treatment with Ang-(1–7) on hypoglycemia during endotoxemia. For this, male Wistar Hannover rats underwent stereotaxic surgery for intracerebroventricular (i.c.v.) administration of Ang-(1–7) and cannulation of the jugular vein for lipopolysaccharide (LPS) injection. Our results demonstrate that LPS was capable of inducing hypoglycemia and that prior central treatment with Ang-(1–7) attenuated this effect. Our data also show that Ang-(1–7) reduced plasma concentrations of TNF-α, IL-1β, IL-6, and nitric oxide, in addition to the decrease and increase of hepatic IL-6 and IL-10 respectively, in animals subjected to systemic inflammation by LPS, resulting in the reduction of systemic and hepatic inflammation, thus attenuating the deleterious effects of LPS on phosphoenolpyruvate carboxykinase protein content. In summary, the data suggest that central treatment with Ang-(1–7) attenuates hypoglycemia induced by endotoxemia, probably through anti-inflammatory action, leading to reestablishing hepatic gluconeogenesis.

Possible Impact of Human β-defensin 1 on sperm motility in infertile men with abnormal sperm parameters

Human β-defensins and interleukins may be auxiliary in sperm maturation. This cross-sectional study aimed to evaluate the expression of Human β-defensins 1 and 2, interleukins (ILs)− 10 and -18 genes in sperm, as well as seminal plasma levels of these two cytokines in subfertile men with different types of sperm abnormalities compared to those with normozoospermic men. Participants were separated into two experimental groups: the control group (n = 25) and the group with sperm abnormalities (SA) (n = 45). SA participants were further subdivided into the following groups with n = 15 individuals each: Teratozoospermia (T), Asthenoteratozoospermia (AT), and Oligoasthenoteratozoospermia (OAT) groups. The quantitative real-time polymerase chain reaction was used to quantify the mRNA levels of hBDs 1 and 2, IL-10, and IL-18 in sperm. The seminal plasma concentrations of IL-10 and IL-18 were measured by using the enzyme-linked immunosorbent assay technique. The mRNA expression of hBD-1 and IL-10 showed a significant decrease in the OAT compared to the controls (P < 0.0001 and P = 0.02, respectively). The lowest seminal plasma concentration of IL-10 belonged to the OAT (P = 0.04). ROC curve analysis showed a sensitivity, specificity, and cutoff value of 82.35%, 86.67%, and 0.63 for hBD-1 levels, respectively. A positive and significant correlation was found between hBD-1 expression and sperm motility and IL-10 expression rate and normal sperm morphology.Therefore, hBD-1 could be considered as the alternative biomaterial to pre-treatments of infertile men with abnormal sperm parameters, specifically OAT men, which led to improving the assisted reproduction success rate.

Differential changes in expression of inflammatory mRNA and protein after oleic acid-induced acute lung injury

Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. Methods: Nineteen juvenile female swine were included in the study. ARDS defined by a PaO2/FiO2 ratio < 300 was induced by continuous oleic acid infusion. Arterial blood was drawn before and during oleic acid infusion, and when ARDS was established. Cytokine expression in WBC was analyzed by RT-qPCR and plasma protein expression by ELISA. Results: The median concentration of IFN-γ mRNA was estimated to be 59% (p = 0.006) and of IL-6 to be 44.4% (p = 0.003) of the baseline amount. No significant changes were detected for TNF-α, IL-17, and IL-10 mRNA expression. In contrast, the concentrations of plasma IFN-γ and IL-6 were significantly higher (p = 0.004 and p = 0.048 resp.), and TNF-α was significantly lower (p = 0.006) at ARDS compared to baseline. Conclusions: The change of proinflammatory cytokines IFN-γ and IL-6 expression is different comparing mRNA and plasma proteins at oleic acid-induced ARDS compared to baseline. The migration of cells to the lung may be the cause for this discrepancy.

Plasma concentrations of IL-8, IFN-γ and IL-1β in schizophrenia patients with subgroup analysis of first episode drug naïve patients

IntroductionIncreased plasma concentrations of proinflammatory cytokines are found in chronic schizophrenia patients, patients with first episode and in individuals with high risk for psychosis. The most replicated findings are increased concentrations of IL-6, TNF-α and IL-1β through different phases of the disorder while the results for two important proinflammatory cytokines IL8 and IFN-γ were not consistent.ObjectivesPrimary objective of this study was to assess differences in concentrations of IL-8, IFN-γ and IL-1β between schizophrenia patients and healthy controls, Secondary objective was to explore differences in first episode drug naïve patients.MethodsWe measured plasma concentrations of IL-8, IFN-γ and IL-1β in 64 healthy controls and 64 schizophrenia patients during acute exacerbation and remission phase. 25% were drug naive first episode schizophrenia patients. The patients were matched by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.Results Levels of IL-8 were significantly lower in patients with schizophrenia in acute phase and remission compared to healthy controls (p=0,009 for acute phase and p=0,020 for remission). There was no significant difference in the levels of INF-γ and IL-β between schizophrenia in acute phase and remission and healthy controls (p&gt;0,05). In schizophrenia patients there was no difference in the levels of INF-γ, IL-β and IL-8 between acute phase, remission and healthy controls (p&gt;0,05). There was no difference in plasma levels of IL-8, IFN-γ and IL-1β between first episode drug naïve and previously treated schizophrenia patients.Conclusions Our research did not find disturbance of plasma levels of IFN-γ and IL-1β in schizophrenia patients, although the increase of IL-1β was the most replicated finding up to date. Interestingly and contrary to expected the finding of significantly decreased levels of IL-8 in schizophrenia patients requires further research since IL-8 plays a vital role in the inflammatory pathway and may be implicated in cognitive dysfunction.Disclosure of InterestNone Declared

Determination of Early Diagnostic Biomarkers of Renal Dysfunction After Cardiopulmonary Bypass: miR-21 and miR10a Mediated Postoperative Inflammation

Objective: Acute renal failure (ARF) prevalence is high among patients who undergo cardiopulmonary bypass (CPB), and this condition can only be diagnosed via serum creatinine level (sCr) conventionally within 48 hours. Therefore, we need early novel diagnosis biomarkers to start preventive treatment of ARF. For that reason, we aimed to analyze if plasma miR-21 derived from heart, correlates with kidney- enriched miR-10a during inflammatory IL-6, IL-1β, and TNF-α response in terms of acute renal failure 30 minutes after CPB.&#x0D; Methods: Patients (n=46, Female:8 and Male:38), aged 61.08±9.41, who underwent CPB surgery were included. Blood samples were collected during the pre – and post-CPB (30 minutes after CPB). Demographic data of all cases were collected. Quantification of expression levels of miR-21 and miR-10a was done via quantitative PCR (qPCR). Determination of plasma concentration of relevant cytokines, IL-6, IL-1β, and TNF-α was done via ELISA.&#x0D; Results: The circulating level of miR-21 during post-CPB period (-11.78±6.98) was significantly higher (p≤0.05) than pre-CPB period (-6.55±7.11), but there was no significant change (p&gt;0.05) in the circulating level of miR-10a between pre – (-12.22±3.55) and post-CPB (-11.60±3.36) periods. When we compared the mean ΔΔCt values of miR-21 and miR-10a, downregulation was observed in the expression level of miR-10a (0.62±3.77) whilst the expression level of miR-21 (-5.22±7.25) was upregulated (p≤0.05). The levels of plasma concentration of IL-6 (2.74±2.50 ng/l) and TNF-α (83.63±9.33 ng/l) were increased during post-CPB period (both were ***p

Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition.

Subclinical inflammation and cognitive deficits have been separately associated with asymptomatic Plasmodium falciparum infections in schoolchildren. However, whether parasite-induced inflammation is associated with worse cognition has not been addressed. We conducted a cross-sectional pilot study to better assess the effect of asymptomatic P. falciparum parasitemia and inflammation on cognition in Kenyan schoolchildren. We enrolled 240 children aged 7-14 years residing in high malaria transmission in Western Kenya. Children performed five fluid cognition tests from a culturally adapted NIH toolbox and provided blood samples for blood smears and laboratory testing. Parasite densities and plasma concentrations of 14 cytokines were determined by quantitative PCR and multiplex immunoassay, respectively. Linear regression models were used to determine the effects of parasitemia and plasma cytokine concentrations on each of the cognitive scores as well as a composite cognitive score while controlling for age, gender, maternal education, and an interaction between age and P. falciparum infection status. Plasma concentrations of TNF, IL-6, IL-8, and IL-10 negatively correlated with the composite score and at least one of the individual cognitive tests. Parasite density in parasitemic children negatively correlated with the composite score and measures of cognitive flexibility and attention. In the adjusted model, parasite density and TNF, but not P. falciparum infection status, independently predicted lower cognitive composite scores. By mediation analysis, TNF significantly mediated ~29% of the negative effect of parasitemia on cognition. Among schoolchildren with PCR-confirmed asymptomatic P. falciparum infections, the negative effect of parasitemia on cognition could be mediated, in part, by subclinical inflammation. Additional studies are needed to validate our findings in settings of lower malaria transmission and address potential confounders that could affect both inflammation and cognitive performance.