Plasma Concentrations Of Interleukin-6 Research Articles

Osteoprotegerin and Inflammation in Incident Peritoneal Dialysis Patients.

Objectives: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). Methods: The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. Results: Plasma concentration of OPG did not correlate with dialysate OPG level (Rs = 0.04, p = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) (Rs = 0.41; p = 0.01), plasma IL-6 (Rs = 0.38; p = 0.01) and plasma hsCRP (Rs = 0.35; p = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) (Rs = 0.37; p = 0.02) and dialysate IL-6 levels (Rs = 0.44; p = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) (ß = +0.38, p = 0.006), higher plasma hsCRP (ß = +0.32, p = 0.02) and older age (ß = +0.35, p = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 (ß = +0.37, p = 0.02) were independent determinants of higher dialysate OPG concentration. Conclusions: Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.

A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.

Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse model that integrated clinically relevant genetic (catechol-O-methyltransferase; COMT knockdown) and environmental (stress and injury) factors. Compared with wild-type mice, Comt+/- mice undergoing repeated swim stress and molar extraction surgery intervention exhibited pronounced multisite body pain and depressive-like behavior lasting >3 months. Comt+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent nociceptors innervating hindpaw and low back sites and increased plasma concentrations of norepinephrine and pro-inflammatory cytokines interleukin-6 (IL-6) and IL-17A. The pain and depressive-like behavior were of greater magnitude and longer duration (≥12 months) in females versus males. Furthermore, increases in anxiety-like behavior and IL-6 were female-specific. The effect of COMT genotype × stress interactions on pain, IL-6, and IL-17A was validated in a cohort of 549 patients with CPPCs, demonstrating clinical relevance. Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund's adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics.

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85

ObjectiveTo investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85.MethodsOne hundred patients (four cases excluded) aged 70–85 years, with body mass index 18–24 kg·m−2 and American Society of Anesthesiologists physical status II–III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg−1·h−1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid–binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted.ResultsCompared with group C, MAP was significantly higher at T1–T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia.ConclusionsLow-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury.Trial registrationThis study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

Elevated interleukin-6 in women with binge-eating spectrum disorders.

Binge-eating spectrum disorders (BESD) involve large eating episodes accompanied by a sense of loss of control that occur in individuals with body weights spanning the full body mass index (BMI) spectrum. While research links BESD with peripheral inflammation, this literature is limited by underpowered studies and a failure to control for confounding variables that could promote inflammation independent of dysregulated eating, specifically elevated body adiposity and depression. Our study examined plasma interleukin-6 (IL-6), a marker of peripheral inflammation, in a sample of women with BESD and non-eating disorder controls, controlling for BMI, body adiposity, and depression. Participants (N = 94) included women with BESD (n = 73) or no eating disorder (n = 21) who completed structured clinical interviews in a larger study, selected to represent BMI categories ranging from underweight to obese in both groups. Fasting blood samples were processed for plasma IL-6 concentration via enzyme-linked immunosorbent assays. In addition to assessing group differences in plasma IL-6, exploratory analyses examined associations between IL-6 and biological and clinical markers of BESD. Significantly elevated plasma IL-6 was found in women with BESD, relative to controls, that was not accounted for by BMI, adiposity, or depression. Plasma IL-6 was positively correlated with plasma leptin concentration, clinical assessments of eating disorder severity, and participants' largest self-reported eating episode. Peripheral inflammation is specifically linked to presence of dysregulated eating independently from weight, adiposity, and depression in BESD. Future research should probe the potential role of neuroinflammation in altered eating behavior. This study provides the first demonstration that inflammation, characterized by elevated plasma IL-6 concentration, is uniquely associated with dysregulated eating in a transdiagnostic group of individuals with BESD. A better understanding of whether immune factors contribute to dysregulated eating could help identify novel biological targets for intervention.

Dissociation of blood interleukin spectrum in the patients with accelerated aging and diabetic retinopathy

Diabetic retinopathy is a common complication of diabetes mellitus, especially, in elderly persons, due to growth of this population in many countries. However, involvement of immune system in patients with diabetic retinopathy and into the aging process is not sufficiently covered in the research works. The aim of the present study was to evaluate the contents of systemic interleukins in the patients with diabetic retinopathy with accelerated versus physiological aging.We observed 240 patients aged 60-74 years with diabetic retinopathy and 115 age-matched patients without diabetic retinopathy under clinical conditions. The diagnosis of diabetic retinopathy was assessed in accordance with Clinical Guidelines of the All-Russian Association of Ophthalmologists “Diagnostics and Treatment of Diabetic Retinopathy and Diabetic Macular Edema”. The biological age of the subjects was determined instrumentally, by means of VaSera VS-1500 sphygmomanometer. The contents of interleukins in blood plasma was determined by ELISA technique using the “Protein contour” kit.It was established that the chronological (calendar) age of patients with diabetic retinopathy and without diabetic retinopathy was not significantly different (70.9±0.7 and 70.2±0.8 years old, respectively; p &gt; 0.05). However, the biological age in these groups differed significantly (75.7±1.1 and 72.3±1.0 years old, respectively; p &lt; 0.001), thus suggesting accelerated aging of patients suffering from diabetic retinopathy. Plasma concentrations of interleukins in patients with diabetic retinopathy with accelerated aging, when compared with physiologically aged patients with diabetic retinopathy revealed statistically significant differences for the most analyzed interleukins. A particularly pronounced increase of the blood plasma interleukins in patients with diabetic retinopathy and accelerated aging was revealed for IL-6 (25.7±1.8 pg/mL versus 4.2±0.5 pg/mL in physiologically aged patients with diabetic retinopathy (p &lt; 0.001). A significant increase of interleukin levels among patients with accelerated aging and diabetic retinopathy was found for IL-13 and IL-17. IL-13 contents in the patients with diabetic retinopathy and accelerated aging reached 2.2±0.3 pg/mL versus 0.7±0.2 pg/mL in physiologically aging patients with diabetic retinopathy (p &lt; 0.001). Respectively, the IL-17 levels were 19.8±0.6 pg/mL and 8.4±0.9 pg/mL. The mean concentration of IL-1b, IL-3 among patients with diabetic retinopathy and accelerated aging was also significantly increased. At the same time, in the blood plasma of the prematurely aged patients with diabetic retinopathy, we have revealed a statistically significant decrease of anti-inflammatory interleukins and, especially, IL-10 to 7.4±0.6 pg/mL versus 19.2±0.7 pg/mL (p &lt; 0.001). Therefore, IL-6, IL-8, IL-13, IL-17, IL-4, and IL-10 levels may be used as immunological predictors of accelerated aging in the patients with diabetic retinopathy.

Biomarkers in Endurance Exercise: Individualized Regulation and Predictive Value.

The high interindividual variability of exercise response complicates the efficient use of blood-based biomarkers in sports. To address this problem, a useful algorithm to characterize the individual regulation and predictive value of different candidate markers will be developed. Forty-nine participants completed two identical exercise trials. Blood samples were collected before, immediately after, 3 hours after, and 24 hours after completion of exercise. Plasma concentrations of interleukin (IL-) 1RA, IL-6, IL-8, IL-10, IL-15, creatine kinase (CK), cortisol, c-reactive protein (CRP), lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS) were measured. Individualized regulation was analyzed using k-means clustering and a Group Assignment Quality (GAQ) score. Regression trees with a bootstrapped-aggregated approach were used to assess the predictive qualities of the markers. For most of the markers studied, a distinction can be made between individuals who show a stronger or weaker response to a particular endurance training program. The regulation of IL-6, IL-8, IL-10, and CK exhibited a high degree of stability within the individuals. Regarding the predictive power of the markers, for all dependent variables, the most accurate predictions were obtained for cortisol and IL-8 based on the baseline value. For CK, a good prediction of recovery of maximal strength and subjective feeling of exhaustion can be made. For IL-1RA and TBARS, especially their reregulation can be predicted if the baseline level is known. Focusing individual variations in biomarker responses, our results suggest the combined use of IL-6, IL-8, IL-10, and CK for the personalized management of stress and recovery cycles following endurance exercise.

Hot water immersion is associated with higher thermal comfort than dry passive heating for a similar rise in rectal temperature and plasma interleukin-6 concentration.

To compare the perceptual responses and interleukin-6 (IL-6) concentration following rectal temperature-matched dry heat exposure (DH) and hot water immersion (HWI). Twelve healthy young adults (BMI 23.5 ± 3.6kg/m2; age: 25.8 ± 5.7years) underwent 3 trials in randomised order: DH (air temperature 68.9°C), HWI (water temperature 37.5°C), and thermoneutral dry exposure (CON, air temperature 27.3°C). Blood samples to determine IL-6 plasma concentration were collected; basic affect and thermal comfort, rectal and skin temperature (Tskin) were assessed throughout the intervention. Rectal temperature (Trec) did not differ between DH (end temperature 38.0 ± 0.4°C) and HWI (37.9 ± 0.2°C, P = 0.16), but was higher compared with CON (37.0 ± 0.3°C; P ≤ 0.004). Plasma IL-6 concentration was similar after DH (pre to post: 0.8 ± 0.5 to 1.4 ± 1.5pg·ml-1) and HWI (0.5 ± 0.2 to 0.9 ± 0.6pg·ml-1; P = 0.46), but higher compared with CON (0.6 ± 0.5 to 0.6 ± 0.4pg·ml-1; P = 0.01). At the end of the intervention, basic affect and thermal comfort were most unfavourable during DH (Basic affect; DH: - 0.7 ± 2.9, HWI: 0.8 ± 1.9, CON 1.9 ± 1.9, P ≤ 0.004; Thermal comfort; 2.6 ± 0.8, HWI: 1.4 ± 0.9 and CON: 0.2 ± 0.4; P ≤ 0.004). Mean Tskin was highest for DH, followed by HWI, and lowest for CON (DH: 38.5 ± 1.3°C, HWI: 36.2 ± 0.5°C, CON: 31.6 ± 0.7°C, P < 0.001). The IL-6 response did not differ between DH and HWI when matched for the elevation in Trec. However, thermal comfort was lower during DH compared to HWI, which may be related to the higher Tskin during DH.

No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.

Novel inflammatory biomarkers associated with stroke severity: results from a cross-sectional stroke cohort study

BackgroundStroke is a leading cause of mortality and disability worldwide and its occurrence is expected to increase in the future. Blood biomarkers have proven their usefulness in identification and monitoring of the disease. Stroke severity is a major factor for estimation of prognosis and risk of recurrent events, but knowledge on respective blood biomarkers is still scarce. Stroke pathophysiology comprises a multitude of ischemia-induced inflammatory and immune mediated responses. Therefore, the assessment of an immune-related panel in correlation with stroke severity seems promising.MethodsIn the present cross-sectional evaluation, a set of 92 blood biomarkers of a standardized immune panel were gathered (median 4.6 days after admission) and related to stroke severity measures, assessed at hospital admission of acute stroke patients. Multivariable logistic regression models were used to determine associations between biomarkers and modified Rankin Scale (mRS), linear regression models were used for associations with National Institute of Health Stroke Scale.Results415 patients (mean age 69 years; 41% female) were included for biomarker analysis. C-type lectin domain family 4 member G (CLEC4G; OR = 2.89, 95% CI [1.49; 5.59], padj = 0.026, Cytoskeleton-associated protein 4 (CKAP4; OR = 2.38, 95% CI [1.43; 3.98], padj = 0.019), and Interleukin-6 (IL-6) (IL6; OR = 1.97, 95% CI [1.49; 2.62], padj < 0.001) were positively associated with stroke severity measured by mRS, while Lymphocyte antigen 75 (LY75; OR = 0.37, 95% CI [0.19; 0.73], padj = 0.049) and Integrin alpha-11 (ITGA11 OR = 0.24, 95% CI [0.14, 0.40] padj < 0.001) were inversely associated. When investigating the relationships with the NIHSS, IL-6 (β = 0.23, 95% CI [0.12, 0.33] padj = 0.001) and ITGA11 (β = − 0.60, 95% CI [− 0.83, − 0.37] padj < 0.001) were significantly associated.ConclusionsHigher relative concentrations of plasma CLEC4G, CKAP4, and IL-6 were associated with higher stroke severity, whereas LY75 and ITGA11 showed an inverse association. Future research might show a possible use as therapeutic targets and application in individual risk assessments.

Plasma cytokine levels in spinal surgery with sevoflurane or total intravenous propofol anesthesia – A post hoc analysis of a randomized controlled trial

Surgical tissue trauma stimulates an inflammatory response resulting in increased levels of cytokines which could contribute to acute kidney injury (AKI). It is not clear if anesthetic modality affects this response. We aimed to investigate the role of anesthesia in a healthy surgical population on the inflammatory response and the correlation to plasma creatinine.This study is a post hoc analysis of a published randomized clinical trial. We analyzed plasma from patients who underwent elective spinal surgery randomized to either total intravenous propofol anesthesia (n = 12) or sevoflurane anesthesia (n = 10). The plasma samples were collected before anesthesia, during anesthesia, and 1 h after surgery. Plasma cytokine levels after surgery were analyzed for correlations with duration of surgical insult and change in plasma creatinine concentration.The cytokine interleukin-6 (IL-6) was increased after surgery compared with preoperatively. IL-6 was higher in the sevoflurane group than the propofol group after surgery. No patient developed AKI, but plasma creatinine was increased postoperatively in the sevoflurane group. There was a significant association between surgical time and plasma IL-6 postoperatively. No significant correlation between change in plasma creatinine and IL-6 was detected. The cytokines IL-4, IL-13, Eotaxin, Interferon γ-Induced Protein 10 (IP-10), Granulocyte Colony-Stimulating Factor (G-CSF), Macrophage Inflammatory Protein-1β (MIP-1β), and Monocyte Chemoattractant Protein 1 (MCP-1) were lower postoperatively than before surgery independent of anesthetic modality.This post hoc analysis revealed that plasma IL-6 was increased after surgery and more so in the sevoflurane group than the propofol group. Postoperative plasma IL-6 concentration was associated with surgical time.

Effect of curcumin supplementation on inflammatory status and muscle damage in competitive female soccer players: a placebo-controlled, singleblind, nonrandomized, crossover pilot study.

Curcumin, a major component of turmeric, has anti-inflammatory and antioxidative properties, which are associated with protective effects against muscle damage. This study examined the effects of dietary curcumin on inflammation and muscle damage in female competitive soccer players. A single-blinded, placebo-controlled, nonrandomized, crossover pilot study was conducted. Six competitive female soccer players (20.0 ± 2.0 yearsold) who participated in a 2-week preseason training program were assigned to two conditions: placebo and curcumin. The participants ingested a placebo or curcumin dosage (270 mg/day) during 2 weeks of preseason training, with 1 week of washout. Fasting blood samples were collected under resting conditions before (day 0) and after (day 15) the training period to examine changes in the concentration of interleukin 6 (IL-6), an inflammatory marker, and indices reflective of muscle damage. Curcumin decreased the concentration of IL-6 released (mean decrease, -30.2 ± 28.1%), whereas no decrease was observed in the placebo condition (13.4 ± 17.4%). Changes in plasma IL-6 concentrations were significantly greater in the curcumin condition than in the placebo condition (p &lt; 0.05). However, curcumin supplementation had no significant effects on muscle damage indices. The present study shows that curcumin supplementation could attenuate inflammation, as indicated by IL-6 concentrations, in competitive female soccer players during the training period.

A Single Bout of High Heels Dancing Causes an Increase in Circulating Markers of Muscle Tissue Degradation and MMP-3 in Young Healthy Women.

Prolonged wearing of high heels can cause chronic injury and inflammation. Herein, we investigated the presence of muscle injury, inflammation, and neutrophil function in young women after a single bout of stiletto dance class. Sixteen volunteers (23.4 ± 3.8 years; 61.7 ± 8.1 kg; 23.4 ± 2.3 kg/m2; and 27.2 ± 3.8% body fat) participated in the study. The plasma biomarkers matrix metalloproteinase 3 (MMP-3), muscle damage (myoglobin (Mb), total creatine kinase (CK), and lactate dehydrogenase (LDH)), and inflammation (interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-α), interleukin (IL]-1β, and IL-6) were quantified before and immediately after a single stiletto class (60 min) of moderate intensity. After class, our data showed that the plasma concentration of MMP-3, Mb, and CK increased by 56% (p = 0.04; d = 0.8), 113% (p = 0.007; d = 1.1), and 21% (p < 0.001; d = 0.4), respectively. Reactive oxygen species produced by neutrophils and the plasma concentration of IL-8, TNF-α, IL-1β, and IL-6 were not affected under the study conditions. We concluded that a single bout of stiletto dance class caused muscle damage but did not alter the plasma concentration of proinflammatory cytokines. These findings are crucial in preventing the progress of chronic injuries that are often noted in dancers with synovitis and arthritis.

1 Repeated muscle collections induce few physiological changes in mature sedentary horses

Repeated skeletal muscle collections are often used to determine tissue-specific responses to interventions or stressors but little is known about the physiological impacts of the collections themselves. Twenty-six mature sedentary horses (8 geldings, 18 mares; mean ± SD 9.5 ± 3.5y) were used to test the hypothesis that repeated muscle collections would not impact mitochondrial function or markers of inflammation and muscle damage. Horses were stratified by age and sex and randomly assigned to have gluteus medius samples collected at: 1) 0 and 24 h (n = 7); 2) 0 and 6 h (n = 6); 3) 0, 6, and 12 h (n = 7); or 4) 0, 6, 12, and 24 h (n = 6). Blood was collected from all horses every 6 h for 72 h total, starting 24 h before the first muscle collection. Muscle mitochondrial oxidative phosphorylation and electron transfer (E) capacities were determined via high-resolution respirometry, and mitochondrial volume density and function by citrate synthase (CS) and cytochrome c oxidase activities. Muscle and plasma concentrations of interleukin (IL)- 4, IL-8, IL-10, and tumor necrosis factor (TNF)α were quantified, as well as serum amyloid A (SAA) and cortisol concentrations and creatine kinase (CK) activity. Data were analyzed using linear models in SAS with time as a repeated measure, horse as the subject, time as a fixed effect, and sex when significant. For blood parameters, additional fixed effects includedcollection group and the time × group interaction. Integrative (per mg tissue) E supported by complex II decreased from 0 to 6 h (P = 0.004) but returned to baseline by 12 h post-initial muscle collection. Intrinsic (per unit CS) Leak was greater at 6 than at 0 and 12 h (P < 0.03) but did not differ from 24 h. Activity of CS was greater at 0 than 12 and 24 h (P ≤ 0.02). Regardless of group, serum CK activity was similar from −24 through 0 h but increased in all horses at 6 h and remained elevated through 48 h, peaking at 24 and 30 h post-initial muscle collection (P < 0.05). Geldings had greater serum CK activity and plasma IL-8 concentrations than mares (P ≤ 0.006). Serum cortisol concentrations displayed a circadian pattern throughout the 72-h collection period (P < 0.0001) but were not impacted by tissue collection group. Overall, horses in group 2 (0 and 6 h) had greater SAA concentrations than all other groups (P < 0.006). No other variable was impacted by repeated tissue collections. In unstressed, mature horses, repeated gluteal muscle collections did not profoundly impact local and systemic markers of mitochondrial function, select cytokines, and stress indicators; however, serum CK should be interpreted with caution in studies employing repeated tissue collections.

Alpha-linolenic acid modulates systemic and adipose tissue-specific insulin sensitivity, inflammation, and the endocannabinoid system in dairy cows

Metabolic disorders are often linked to alterations in insulin signaling. Omega-3 (n-3) fatty acids modulate immunometabolic responses; thus, we examined the effects of peripartum n-3 on systemic and adipose tissue (AT)-specific insulin sensitivity, immune function, and the endocannabinoid system (ECS) in dairy cows. Cows were supplemented peripartum with saturated fat (CTL) or flaxseed supplement rich in alpha-linolenic acid (ALA). Blood immunometabolic biomarkers were examined, and at 5–8 d postpartum (PP), an intravenous glucose-tolerance-test (GTT) and AT biopsies were performed. Insulin sensitivity in AT was assessed by phosphoproteomics and proteomics. Peripartum n-3 reduced the plasma concentrations of Interleukin-6 (IL-6) and IL-17α, lowered the percentage of white blood cells PP, and reduced inflammatory proteins in AT. Systemic insulin sensitivity was higher in ALA than in CTL. In AT, the top canonical pathways, according to the differential phosphoproteome in ALA, were protein-kinase-A signaling and insulin-receptor signaling; network analysis and immunoblots validated the lower phosphorylation of protein kinase B (Akt), and lower abundance of insulin receptor, together suggesting reduced insulin sensitivity in ALA AT. The n-3 reduced the plasma concentrations of ECS-associated ligands, and lowered the abundances of cannabinoid-1-receptor and monoglycerol-lipase in peripheral blood mononuclear cells PP. Peripartum ALA supplementation in dairy cows improved systemic insulin sensitivity and immune function, reduced ECS components, and had tissue-specific effects on insulin-sensitivity in AT, possibly counter-balancing the systemic responses.

Intraoperative Enteral Nutrition Feeding in Free-Flap Healing after Reconstruction Surgery for Head and Neck Cancers.

To investigate the beneficial outcomes of intraoperative enteral feeding in free-flap regeneration after extended head andneck cancer resection and flap reconstruction surgery. A pilot randomized, double-blind, placebo-controlled clinical trial. Single tertiary care center. Patients with advanced head andneck cancers requiring radical tumor resections and free-flap reconstruction were randomly assigned to receive intraoperative enteral nutrition feeding (100 kcal/100 mLat 10-20 mL/h) via a nasogastric tube during free-flap reconstruction (n = 28) or continue fasting (n = 28). The primary outcome was impaired free-flap regeneration that required surgical reintervention within 90 days after the operation. Participants were enrolled between April 2020 and January 2022; the 90-day follow-up ended in April 2022. The incidence of total or partial flap failure was similar between the 2 groups (14.2% or n = 4 in each group), but the rate of wound dehiscence or edge necrosis was significantly reduced in the feeding group (n = 6 vs 0 for fasting vs feeding; absolute risk reduction, 25.0% [95% confidence interval, 6.9-43.0]%; p = 0.022). Hospital stay length was shorter (p = 0.042) and hand grip strength was better preserved (p = 0.025) in the feeding group. Plasma concentrations of interleukin (IL)-6 and IL-8 after the operation increased significantly more in the fasting group. Perioperative adverse events did not differ between the 2 groups. Perioperative enteral feeding is a simple, safe, and effective approach to improve perioperative systemic catabolism and proinflammatory reactions, thereby enhancing early wound regeneration after major operations.

Inflammatory phenotype, clinicopathologic variables, and effects of long-term methylene blue in dogs with hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency

To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry results, and describe changes in methemoglobin (MetHb) levels and serum C-reactive protein (CRP) concentrations after long-term per os (PO) methylene blue (MB) therapy. 21 client-owned dogs (CYB5R deficient, n = 10; healthy controls, 11). In this prospective, case-control study, methemoglobin levels were measured using a blood gas analyzer with co-oximetry. Plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were measured using a canine-specific multiplex bead-based assay. Serum CRP concentrations were measured with a canine-specific commercial ELISA kit. Serum CRP concentration and MetHb levels were measured in 6 dogs with CYB5R deficiency after ≥ 60 days of PO MB therapy. As expected, MetHb levels were higher in dogs with CYB5R deficiency compared to controls (P < .001). Plasma TNF-α, IL-6, IL-10, and serum CRP concentrations were no different between CYB5R-deficient and control dogs. Dogs with CYB5R deficiency had lower absolute lymphocyte (P = .005) and eosinophil counts (P = .04) and higher alanine transaminase (P = .04) and alkaline phosphatase activity (P = .02) than controls, but these changes were not clinically relevant. Methemoglobin levels decreased after PO MB therapy (P = .03). These results suggest that otherwise healthy dogs with CYB5R deficiency do not have a constitutive proinflammatory phenotype and clinically relevant abnormalities in hematologic and serum chemistry panels are not expected. Dogs with decreased quality of life attributed to methemoglobinemia from CYB5R deficiency might benefit from PO MB therapy.

ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run

The aim of the study was to reveal whether marathon running influences regulators of lipid metabolism i.e. angiopoietin-like protein 4 (ANGPTL4), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Plasma concentration of ANGPTL4, IL-6, TNF-α and lipids were determined in samples collected from 11 male runners before the marathon, immediately after the run and at 90 min of recovery. Plasma ANGPTL4 increased during exercise from 55.5 ± 13.4 to 78.1 ± 15.0 ng/ml (P < 0.001). This was accompanied by a significant increase in IL-6, TNF-α, free fatty acids (FFA) and glycerol (Gly) and a decrease in triacylglycerols (TG). After 90 min of recovery ANGPTL4 and TG did not differ from the exercise values, while plasma IL-6, TNF-α, FFA and Gly concentration were significantly lower. The exercise-induced increase in plasma concentration of ANGPTL4 correlated positively with the rise in plasma IL-6, TNF-α, FFA and Gly and negatively with the duration of the run. The increase in plasma IL-6 and TNF-α correlated positively with the rise in Gly. Summarizing, marathon running induced an increase in plasma ANGPTL4 and the value was higher in faster runners. The increase in plasma FFA, IL-6 and TNF-α concentration during a marathon run may be involved in plasma ANGPTL4 release, which could be a compensatory mechanism against FFA-induced lipotoxicity and oxidative stress. All of the analyzed cytokines may stimulate lipolysis during exercise.

Inflammatory activation biomarker profile after marathon running and its impact on cardiovascular stress in amateur middle-aged male runners.

Cardiovascular safety of marathon running middle-aged amateurs remains unclear. We previously hypothesized that transient release of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in addition to an acute inflammatory response to exercise, may be the cause. To evaluate the effects of running a marathon on inflammatory biomarkers, and its impact on cardiovascular function. Thirty-three healthy male amateur runners aged ≥50 (mean age: 57 ±7 years) were enrolled in the study. Venous blood samples were obtained before the marathon, just after the race, and 2-4 days and 7 days after the marathon. Using novel single molecule counting (SMC) technology, we measured plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). White blood cell (WBC) count was measured using a certified hematology analyzer. The results were related to previous analyses on cardiovascular stress and endothelial function biomarkers. Transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were used to determine myocardial function. We observed a sharp rise of all studied biomarkers after the race, which subsequently normalized after 2-4 days and stayed within the normal range 7 days after the race. We found no correlation between inflammatory and cardiovascular stress biomarkers. Transthoracic echocardiography and CMR did not show ischemic or inflammatory myocardial damage. Marathon running is associated with a sharp and significant rise in inflammatory and cardiovascular stress biomarkers. We found no connection between immune activation and cardiac biomarker release. Cardiovascular imaging showed no myocardial damage due to ischemia or inflammation.

Prone positioning reduces frontal and hippocampal neuronal dysfunction in a murine model of ventilator-induced lung injury.

Prone positioning is an established treatment for severe acute lung injury conditions. Neuronal dysfunction frequently occurs with mechanical ventilation-induced acute lung injury (VILI) and clinically manifests as delirium. We previously reported a pathological role for systemic interleukin 6 (IL-6) in mediating neuronal injury. However, currently no studies have investigated the relationship between prone or supine positioning and IL-6 mediated neuronal dysfunction. Here, we hypothesize that prone positioning mitigates neuronal injury, via decreased IL-6, in a model of VILI. VILI was induced by subjecting C57BL/6J mice to high tidal volume (35 cc/kg) mechanical ventilation. Neuronal injury markers [cleaved caspase-3 (CC3), c-fos, heat shock protein 90 (Hsp90)] and inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured in the frontal cortex and hippocampus. We found statistically significantly less neuronal injury (CC3, c-Fos, Hsp90) and inflammatory cytokines (IL-6, IL-1β, TNF-α) in the frontal cortex and hippocampus with prone compared to supine positioning (p < 0.001) despite no significant group differences in oxygen saturation or inflammatory infiltrates in the bronchoalveolar fluid (p > 0.05). Although there were no group differences in plasma IL-6 concentrations, there was significantly less cortical and hippocampal IL-6 in the prone position (p < 0.0001), indicating supine positioning may enhance brain susceptibility to systemic IL-6 during VILI via the IL-6 trans-signaling pathway. These findings call for future clinical studies to assess the relationship between prone positioning and delirium and for investigations into novel diagnostic or therapeutic paradigms to mitigate delirium by reducing expression of systemic and cerebral IL-6.

Effect of ultramarathon running on iron metabolism.

Iron is a vital trace element for energy production and oxygen transportation; importantly, it is essential to athletic performance. Maintaining iron balance is tightly controlled at systemic and cellular levels. This study aimed to determine serum iron tests, hepcidin levels, and cellular iron import and export activities in peripheral blood mononuclear cells (PBMCs) in ultramarathon runners to elucidate the association of systemic inflammation response and iron metabolism. Sixteen amateur runners were enrolled. Blood samples were taken 1 week before, immediately, and 24 h after the run. Plasma hepcidin levels were measured by enzyme-linked immunosorbent assay. The expression levels of divalent metal iron transporter 1 (DMT1), ZRT/IRT-like protein 14 (ZIP14), transferrin receptor 1 (TfR1), and ferroportin (FPN) in PBMCs were measured using real-time quantitative reverse transcription-polymerase chain reaction. Serum iron concentrations and transferrin saturation significantly decreased immediately after the race and dramatically recovered 24 h post-race. Serum ferritin levels had a statistically significant rise immediately after the race and remained high 24 h after the completion of the race. Ultramarathons were associated with increased plasma interleukin-6 concentrations corresponding to the state of severe systemic inflammation and therefore boosted plasma hepcidin levels. The expression levels of DMT1 and FPN mRNA were markedly decreased immediately and 24 h after the race. The ZIP14 and TfR1 mRNA expression in PBMCs significantly decreased immediately after the race and returned to the baseline level at 24 h post-race. Positive significant correlations were observed between plasma hepcidin and ferritin levels. Iron homeostasis and systemic inflammatory response are closely interconnected. Cellular iron import and export mRNA activities in PBMCs were acutely inhibited during an ultramarathon.