Serum Inflammatory Cytokine Concentrations Research Articles

Dexmedetomidine Alleviates Ischemia/Reperfusion-Associated Acute Kidney Injury by Enhancing Autophagic Activity via the α2-AR/AMPK/mTOR Pathway.

Dexmedetomidine (DEX) reportedly protects against ischemia-reperfusion (I/R) injury and associated damage to the kidneys, but the underlying mechanisms have yet to be established. Unilateral nephrectomy was performed in Wistar rats, and the remaining kidney was clamped for 1 h prior to reperfusion to establish an experimental model system. These animals were then randomized into Sham, DEX + Sham, DEX + I/R, ATI (Altepamizole, α2-adrenergic receptor inhibitor) + DEX + I/R, and 3-MA (3-methyladenine, autophagy inhibitor) + DEX + I/R groups. Serum renal function biomarkers, acute kidney injury (AKI) histopathological scores, serum inflammatory factors, redox biomarkers, markers of autophagic flux, and autophagosome numbers were assessed. Levels of proteins related to the autophagic pathway, including mTOR and AMPK, were also analyzed. Serum creatinine and urea nitrogen levels in the I/R group were significantly elevated over those in sham control rats, as were AKI scores, serum inflammatory cytokine concentrations (IL-6, IL-1β, and TNF-α), and serum levels of the oxidative stress biomarker malondialdehyde (MDA). All of these parameters were significantly reduced in the DEX + I/R group relative to I/R model rats. I/R group rats also exhibited significant decreases in renal levels of autophagic flux-related biomarkers and autophagosome numbers relative to sham controls, while DEX administration partially restored normal autophagic flux in these rats. Acute I/R also suppress the expression of AMPK in the kidney while increasing mTOR expression, and DEX reversed these effects. The beneficial impact of DEX on I/R-associated AKI was ablated by ATI or 3-MA administration. These analyses provide strong evidence for the ability of DEX to protect against I/R-associated AKI via the α2-AR/AMPK/mTOR pathway-mediated enhancement of autophagic activity.

Lipoamide Alleviates Oxidized Fish Oil-Induced Host Inflammatory Response and Oxidative Damage in the Oviduct of Laying Hens.

Fish oil (FO) is an important source of lipid in functional food and aquafeeds. However, the harmful effects of oxidized fish oil (OFO) on host metabolism and reproductive health are not yet clear. In addition, lipoamide (LAM) has been widely studied as an agent for alleviating various diseases associated with oxidative disruption. Therefore, in the current study, to investigate the effects of LAM in alleviating OFO-induced decline in reproductive performance and oxidative damage to the oviduct in laying hens. We constructed a 1% fresh FO model, a 1% OFO model, and a LAM model with 1% OFO (OFO + LAM) added at 100 mg/kg to explore the antioxidant effect of LAM. Herein, these results were evaluated by breeding performance, immune responses, estrogen, and antioxidant indices of serum samples, as well as the number of follicles and antioxidant parameters of oviducts. From the results, compared with the FO group, OFO significantly decreased the egg-laying rate, increased the contents of total protein (TP) and inflammatory factors [tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, and interferon γ (INF-γ)], and reduced the concentrations of anti-oxidation [total antioxidant (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), glutathione reductase (GR), catalase (CAT), and hydroxyl radical scavenging activity (HRSA)] in serum samples, as well as reduced the levels of anti-oxidation indexes in oviduct tissues (p < 0.05). Of note, the supplementation of LAM could significantly increase the laying performance, improve the levels of serum immunoglobulins (IgA, IgG, and IgM), serum estrogen [progesterone (P) and estradiol (E2)], and serum antioxidant parameters (T-AOC, T-SOD, GSH-Px, GSH, GR, CAT, and HRSA) and decrease the concentrations of serum inflammatory cytokines (TNF-α, IL-6, IL-8, and INF-γ) in laying hens following OFO administration (p < 0.05). In addition, LAM could dramatically increase the contents of antioxidant factors (p < 0.05) in oviducts and enhance the secretion capacity of the uterine part. Taken together, OFO caused host metabolic dysfunction, oxidative damage, uterine morphological abnormalities, and alterations of ovarian function. These results suggested that LAM administration could alleviate host metabolic dysfunctions and inflammatory damage, and then ameliorate oxidative damage in the oviduct induced by OFO, ultimately improving reproductive function.

A Meta-Analysis of Randomized Controlled Trials of the Effects of Soy Intake on Inflammatory Markers in Postmenopausal Women

BackgroundElevated concentrations of serum inflammatory cytokines, specifically TNF-α and IL-6, as well as C-reactive protein (CRP), are commonly observed after menopause. ObjectivesBecause soy isoflavones may have some anti-inflammatory potential, the aim of the present systematic review and meta-analysis of randomized controlled trials (RCTs) was to explore whether soy intake affects serum markers of inflammation in postmenopausal women. MethodsPubMed, Web of Science, and the Cochrane Library were systematically searched up to August 2020. All RCTs that met the following criteria were included: 1) studies of the effects of soy intake on inflammatory markers; 2) any date of publication; 3) conducted on postmenopausal women; 4) with sufficient quantitative data for meta-analysis. Effect sizes were expressed as weighted mean differences (WMDs) and 95% CIs. A total of 24 RCTs assessing the effects of soy intake on serum concentrations of CRP, TNF-α, and IL-6 were included in the analysis. A random-effects model was used to determine the overall effect. ResultsSoy supplementation significantly reduced CRP by 0.11 mg/L in postmenopausal women (95% CI: −0.22, −0.004 mg/L; P = 0.0414), but did not affect IL-6 or TNF-α. Significant reductions in CRP concentration occurred when natural soy products were given (WMD: −0.23 mg/L; 95% CI: −0.29, −0.17 mg/L; P < 0.001). This is equivalent to a ∼9% reduction in CRP concentration from baseline. ConclusionsAlthough our meta-analysis found evidence that soy products significantly reduce CRP concentrations in postmenopausal women, the mechanisms by which soy foods and their constituents affect inflammatory biomarkers still need to be clarified.This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020179232.

Effects of maternal folic acid supplementation during pregnancy on infant neurodevelopment at 1month of age: a birth cohort study in China.

This study aimed to explore effects of maternal folic acid (FA) supplementation during pregnancy on neurodevelopment in 1-month-old infants and to determine whether effects may be related to maternal circulating inflammatory cytokine concentrations. This birth cohort study recruited 1186 mother-infant pairs in Tianjin, China, between July 2015 and July 2017. The women completed interviewer-administered questionnaires on their lifestyles and FA supplementation during pregnancy. Neurodevelopment was assessed in 1-month-old infants using a standard neuropsychological examination table. In 192 women, serum homocysteine (Hcy) and inflammatory cytokine concentrations were measured at 16-18weeks of gestation. The infants whose mothers took FA supplements during pregnancy had a significantly higher development quotient (DQ) compared with those whose mothers were non-users (P < 0.05). After adjustment for maternal characteristics, supplementary FA use for 1-3months, 3-6months, and > 6months were associated with the increases of 7.7, 11.0, and 7.4 units in the scale of infant DQ score compared with women reporting no supplement use, respectively (P < 0.05). FA supplementation was associated with a decreased serum concentration of Hcy (β = [Formula: see text] 0.19), which was correlated with women's serum inflammatory cytokine concentrations at 16-18weeks of gestation (β = 0.57). Serum inflammatory cytokine concentrations were inversely related to DQ score in the 1-months-old offspring (β = [Formula: see text] 0.22). Maternal FA supplementation during pregnancy favors neurodevelopment in the offspring at 1-month-old. This association may be mediated by changes in serum Hcy and inflammatory cytokine concentrations throughout pregnancy.

Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI.

This study aimed to evaluate whether folic acid supplementation would improve cognitive performance by reducing serum inflammatory cytokine concentrations. This RCT was performed in Tianjin, China. Participants with mild cognitive impairment (MCI) were randomly assigned to the folic acid (400 μg/day) or conventional treatment groups. Neuropsychological tests were administered, and folate, homocysteine, vitamin B12, IL-6, TNF-α, Aβ-42, and Aβ-40 were measured at baseline and at 6- and 12-month time points.152 participants (folic acid: 77, conventional: 75) completed the trial. Significant improvements in folate (ηp2 = 0.703, P = 0.011), homocysteine (ηp2 = 0.644, P = 0.009), Aβ-42 (ηp2 = 0.687, P = 0.013), peripheral IL-6 (ηp2 = 0.477, P = 0.025), TNF-α (ηp2 = 0.709, P = 0.009) levels were observed in folic acid group compared with conventional group. Folic acid supplementation improved the Full Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P = 0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months compared with conventional treatment. Based on these findings, daily oral administration of a 400-μg folic acid supplement to MCI subjects for 12 months can significantly improve cognitive performance and reduce peripheral inflammatory cytokine levels.

Application effect of abdomen hot compression of the mirabilite hot compression bag on the treatment of severe acute pancreatitis

Objective To observe the application effect of the self-designed mirabilite hot compression bag on the treatment of severe acute pancreatitis. Methods Seventy severe acute pancreatitis patients who were treated in Hepatopancreatobiliary Surgery Center, Taihe Hospital Affiliated with Hubei University of Medicinein the city of Shiyan in Hubei Province from June of 2013 to February of 2016 were randomly divided into the controlgroup (n=35) and the observation group (n=35) based on the sequence of diagnosis and treatment. Besides the conventional treatment, the patients in the control group received the conventional external application of mirabilite on the abdomen, while the patients in the observation group received abdomen hot compression of the self-designed mirabilite hot compression bag. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and the concentrations of seruminflammatory cytokines on the 1st, 3rd, 6th, 9th day after the admission were compared between the two groups. The incidence rate of the high intra-abdominal pressure, the recovery time of intestinal function andthe average length of stay were analyzed and compared between the two groups. Results On the 1st day after the admission theAPACHE Ⅱ score, the concentrations of C-reactive protein (CRP), interleukin-1(IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF)in the serum were not significantly different between the two groups (P>0.05). On the 3rd day after the admission, the APACHE Ⅱ score, the concentrations of CRP, IL-1 and TNF in the serum in the observation group were significantly lower compared to the control group (P 12 cm H2O), while there were 11 patients with high intra-abdominal pressure in the control group. The intra-abdominal pressure difference was significant (χ2=4.158, P=0.041). The recovery time of intestinal function was (4.9±0.8)days and (5.5±0.8)days in the observation group and the control group, respectively(t=2.899, P<0.05). The average length of stay in the observation group and the control group was (13.1±2.1)days and (15.4±3.9)days, respectively(t=3.129, P<0.05). Conclusions Hot compression of the mirabilite hot compression bag improves the recovery of intestinal function, decreases the concentrations of CRP, IL-1, IL-6 and TNF in the serum, reduces the incidence rate of high intra-abdominal pressure and shortens the length of stay in severe acute pancreatitis patients. Key words: Severe acute pancreatitis; Traditional Chinese medical nursing; Mirabilite hot compression bag

Relationship between deep subcutaneous abdominal adipose tissue and metabolic syndrome: a case control study.

BackgroundThe deep subcutaneous adipose tissue (dSAT) is closely related to the obesity-associated complications similarly to the characteristics of visceral adipose tissue (VAT). However, the association between dSAT and metabolic syndrome (MS) is unclear. The purpose of our study was to evaluate the association of distinct abdominal adipose tissue with the cardiometabolic risk factors and MS.MethodsAbdominal computed tomography (CT) images were obtained in 365 asymptomatic subjects (187 subjects with MS and 178 without MS). The axial images segmented into superficial and deep SAT by manually tracing the fascia superficialis at L4–5 levels. The concentrations of serum inflammatory cytokines and adipokines were also measured.ResultsThe MS group had significantly lower adiponectin levels but significantly higher levels of resistin, leptin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule (ICAM), monocyte chemotactic protein-1 (MCP-1), and oxLDL than the control group (p < 0.05). All inflammatory cytokines and adipokines were associated with the sum of VAT and dSAT areas (VDAT) (P for trend < 0.05), but no significant correlation was found between inflammatory cytokines and sSAT. dSAT was significantly associated with MS in both men and women (OR 2.371; p < 0.001) whereas the ORs between sSAT and MS were not significant (p = 0.597). The age-adjusted ORs between VDAT and MS (OR of 8.359 in men and 3.183 in women, p < 0.001) were higher than those of VAT (OR of 7.941 in men and 2.570 in women, p < 0.05) and dSAT (OR of 2.954 in men and 1.856 in women, p < 0.05).ConclusionsWe demonstrated that dSAT was associated with increased inflammation and oxidative stress, suggesting that dSAT is an important determinant of MS. Therefore, abdominal subcutaneous fat should be considered as two functionally distinct compartments rather than a single entity.

Myocardial Dysfunction in Severe Sepsis and Septic Shock

In vitro studies suggested that circulating inflammatory cytokines cause septic myocardial dysfunction. However, no in vivo clinical study has investigated whether serum inflammatory cytokine concentrations correlate with septic myocardial dysfunction. Repeated echocardiograms and concurrent serum inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and cardiac biomarkers (high-sensitivity [hs] troponin-T and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) were examined in 105 patients with severe sepsis and septic shock. Cytokines and biomarkers were tested for correlations with systolic and diastolic dysfunction, sepsis severity, and mortality. Systolic dysfunction defined as reduced left ventricular ejection fraction (LVEF) < 50% or < 55% and diastolic dysfunction defined as e'-wave < 8 cm/s on tissue-Doppler imaging (TDI) or E/e'-ratio were found in 13 (12%), 24 (23%), 53 (50%), and 26 (25%) patients, respectively. Forty-four patients (42%) died in-hospital. All cytokines, except IL-1, correlated with Sequential Organ Failure Assessment and APACHE (Acute Physiology and Chronic Health Evaluation) II scores, and all cytokines predicted mortality. IL-10 and IL-18 independently predicted mortality among cytokines (OR = 3.1 and 28.3, P = .006 and < 0.0001). However, none of the cytokines correlated with LVEF, end-diastolic volume index (EDVI), stroke-volume index (SVI), or s'-wave and e'-wave velocities on TDI (Pearson linear and Spearman rank [ρ] nonlinear correlations). Similarly, no differences were found in cytokine concentrations between patients dichotomized to high vs low LVEF, EDVI, SVI, s'-wave, or e'-wave (Mann-Whitney U tests). In contrast, NT-proBNP strongly correlated with both reduced LVEF and reduced e'-wave velocity, and hs-troponin-T correlated mainly with reduced e'-wave. Unlike cardiac biomarkers, none of the measured inflammatory cytokines correlates with systolic or diastolic myocardial dysfunction in severe sepsis or septic shock.

Five-Year Outcomes after Oxandrolone Administration in Severely Burned Children: A Randomized Clinical Trial of Safety and Efficacy

Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy. Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored. Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration. Administration of oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.

The effect of caspase-3 inhibitor on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection in mice

To observe the effects of caspase-3 inhibitor Ac-DEVD-CHO on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection in mice. One hundred and two male C57BL/6 mice were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. The animals were assigned into three equal groups (n=34) according to random number table: sham group, model group, and caspase-3 inhibitor (CI) group. Thirty minutes before CLP, Ac-DEVD-CHO (4 μg/g) was injected subcutaneously in CI group. The levels of blood urea nitrogen (BUN) and creatinine (Cr) were determined, and the concentrations of tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-10) were measured by enzyme linked immunosorbent assay (ELISA), the renal cell apoptosis rate was determined by flow cytometry and the expression of caspase-3 mRNA was determined by real time reverse transcription-polymerase chain reaction (RT-PCR) at 6, 12 and 24 hours after operation. The 4-day and 7-day survival rates of three groups of mice were observed. Compared with sham group, the concentrations of serum BUN, TNF-α, IL-6, IL-10 and the renal cell apoptosis rates, the caspase-3 mRNA expression were increased significantly at all time points after CLP, the concentrations of serum Cr were increased significantly at 6 hours, with the 4-day and 7-day survival rates were decreased significantly. Compared with model group, in CI group, the concentrations of serum BUN were decreased significantly at all time points after operation and those of Cr were decreased significantly at 6 hours, then restored to those of the sham group at 12 hours and 24 hours; the concentrations of serum TNF-α, IL-6 were decreased and those of IL-10 elevated significantly at all time points [TNF-α (μg/L) 6 hours: 436.2±64.2 vs. 653.6±8.9, 12 hours: 233.4±85.4 vs. 579.7±137.1, 24 hours: 151.0±90.3 vs. 551.0±119.8; IL-6 (μg/L) 6 hours: 1 033.2±345.8 vs. 1 595.3±159.4, 12 hours : 366.3±68.3 vs. 1 330.7±249.8, 24 hours: 241.2±208.4 vs. 815.3±572.7; IL-10 (μg/L) 6 hours : 33.6±10.4 vs. 26.6±4.5, 12 hours: 37.2±5.0 vs. 24.5±4.3, 24 hours: 38.3±5.5 vs. 18.2±1.6, all P<0.05]; the renal cell apoptosis rate and the expression of caspase-3 mRNA were decreased significantly at all time points [apoptosis rates 6 hours: (13.9±3.2)% vs. (18.3±1.4)%, 12 hours: (10.5±3.6)% vs. (15.9±3.5)%, 24 hours: (8.4±1.8)% vs. (12.5±2.1)%; caspase-3 mRNA 6 hours: 1.95±0.16 vs. 3.84±0.35, 12 hours: 1.89±0.19 vs. 3.97±0.73, 24 hours : 2.01±0.20 vs. 4.97±0.24, all P<0.05]. The 4-day survival rate of CI group was improved (80% vs. 20%), but that of 7-day did not change (20% vs. 20%). The modulation of caspase-3 inhibitor on the concentrations of serum inflammatory cytokines in sepsis related acute kidney injury induced by peritoneal cavity infection may be associated with a decrease in renal cell apoptosis by Ac-DEVD-CHO.

Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats

BackgroundInflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes.MethodsWe investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-α, interleukin [IL]-1β and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age).ResultsSerum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-κB expression in the skeletal muscle of OLETF rats.ConclusionThese results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

Trans-11 Vaccenic Acid Dietary Supplementation Induces Hypolipidemic Effects in JCR:LA-cp Rats

Trans-11 vaccenic acid [VA; 18:1(n-9)] is a positional and geometric isomer of oleic acid and is the precursor to conjugated linoleic acid (CLA) in humans. Despite VA being the predominant trans monoene in ruminant-derived lipids, very little is known about its nutritional bioactivity, particularly in conditions of chronic metabolic disorders, including obesity, insulin resistance, and/or dyslipidemia. The aim of this study was to assess the potential of VA to improve dyslipidemia, insulin sensitivity, or inflammatory status in obese and insulin-resistant JCR:LA-cp rats. The obese rats and age-matched lean littermates were fed a control diet or a control diet supplemented with 1.5% (wt:wt) VA for a period of 3 wk. The incorporation of VA and subsequent conversion to CLA in triglyceride was measured in adipose tissue. Glucose and insulin metabolism were assessed via a conscious adapted meal tolerance test procedure. Plasma lipids as well as serum inflammatory cytokine concentrations were measured by commercially available assays. VA supplementation did not result in any observable adverse health effects in either lean or obese JCR:LA-cp rats. After 3 wk of feeding, body weight, food intake, and glucose/insulin metabolism did not differ between VA-supplemented and control groups. The incorporation of VA and CLA into adipose triglycerides in obese rats fed VA increased by 1.5-fold and 6.5-fold, respectively, compared with obese rats fed the control diet. The most striking effect was a 40% decrease (P < 0.05) in fasting triglyceride concentrations in VA-treated obese rats relative to obese controls. Serum Il-10 concentration was decreased by VA, regardless of genotype (P < 0.05). In conclusion, short-term dietary supplementation of 1.5% VA did not result in any detrimental metabolic effects in JCR:LA-cp rats. In contrast, dietary VA had substantial hypo-triglyceridemic effects, suggesting a new bioactivity of this fatty acid that is typically found in ruminant-derived food products.