Serum IL-36ß levels are associated with Insulin sensitivity in paediatric patients with obesity.

Although the orchestrating role of Interleukin-36 cytokines in regulating inflammation at barrier tissue sites, is well established, whether they play a significant role in the settings of metabolic health and disease, has yet to be fully established. Several recent studies have demonstrated that IL-36 cytokine expression is elevated among adult patients with obesity, and can play roles in regulating both insulin sensitivity and driving inflammation. In this report, we have extended these analyses to paediatric patients and identified an association between elevated serum levels of expression of the specific Interleukin-36 subfamily member, IL-36ß, among children with obesity displaying insulin sensitivity, compared to children with obesity who are insulin resistant. While these data further indicate a possible protective role for IL-36 in metabolic health, they also differ with previous findings from an adult patient cohort, where elevated levels of the related cytokine, IL-36γ, were found to occur in association with improved metabolic health. While highlighting important differences between paediatric and adult patient cohorts in the context of metabolic disease associated with obesity, these data underscore the need for a deeper mechanistic analysis of the role of IL-36 cytokines in disease.

Insights into IL-1 family cytokines in kidney allograft transplantation: IL-18BP and free IL-18 as emerging biomarkers.

Proinflammatory cytokines and their inhibitors are involved in the regulation of multiple immune reactions including response to transplanted organs. In this prospective study, we evaluated changes in serum concentrations of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-1RA, IL-18, IL-18BP, and IL-36 beta) in 138 kidney allograft recipients and 48 healthy donors. Samples were collected before transplantation and then after one week, three months and one year, additional sera were obtained at the day of biopsy positive for acute rejection. We have shown, that concentrations of proinflammatory members of the IL-1 family (IL-1ß, IL-18, IL-36 ß) and anti-inflammatory IL-18BP decreased immediately after the transplantation. The decline of serum IL-1RA and IL-1α was not observed in subjects with acute rejection. IL-18, including specifically its free form, is the only cytokine which increase serum concentrations in the period between one week and three months in both groups of patients without upregulation of its inhibitor, IL-18BP. Serum concentrations of calculated free IL-18 were upregulated in the acute rejection group at the time of acute rejection. We conclude that IL-1 family cytokines are involved mainly in early phases of the response to kidney allograft. Serum concentrations of free IL-18 and IL-18BP represent possible biomarkers of acute rejection, and targeting IL-18 might be of therapeutic value.

Interleukin-1 family cytokines and soluble receptors in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease, characterized by clinical inflammation of the hair follicle with the recurrence of abscesses, nodules, and tunnels. Recently, several studies suggested a role of IL-1 family (IL-1F) cytokines in eliciting and sustaining the disease. The aim of this work is to perform a comprehensive analysis of IL-1F cytokines, soluble inhibitors and receptors in a cohort of HS patients not treated with biological agents. Sixteen patients affected by HS and 16 healthy controls were recruited; clinical data were collected and disease severity evaluated by means of the International HS Severity Score System (IHS4). Serum levels of IL-1F cytokines, inhibitors and receptors were measured using a Multiplex Assays. IL-18 and free IL-18 levels were significantly higher in patients vs controls. Among soluble inhibitors, IL-1Ra, IL-1R2 and ST2/IL-1R4 were significantly increased. IL-18, free IL-18 and IL-33 levels are strongly correlated with IHS4. Also the inhibitors IL-1Ra and IL-18BP show a correlation with IHS4. The data obtained in this study confirm the involvement of IL-1F cytokines in mediating the disease and determining its severity and suggest a possible role for IL-18 as novel serum biomarker of active disease.

The Clinical Significance of Serum Interleukin-36α Levels in Patients with Gout.

BACKGROUND: Gout is a chronic inflammatory diseases caused by monosodium urate crystal deposition. However, the role of interleukin (IL)-36 in gout has not dbeen elucidated. METHODS: We enrolled 75 subjects, including 20 healthy controls (HC), 30 patients with acute gout attack and 25 patients in remission. Baseline data were obtained through clinical interrogation and laboratory data were obtained through tests of blood samples. Serum levels of IL-36α were detected using enzyme-linked immunosorbent assay. Spearman correlation analysis was used to investigate the correlation of IL-36α with other parameters. The diagnostic value of IL-36α was demonstrated using a receiver operating characteristic curve. RESULTS: The serum IL-36α level of gout patients in acute attack and remission stage was significantly higher than that of HC. Serum IL-36α was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST). Serum amyloid A (SAA) levels positively correlated with C-reactive protein levels and erythrocyte sedimentation rates. Glutamyl transpeptidase levels positively correlated with AST and ALT levels. CONCLUSION: In conclusion, serum IL-36α levels were elevated in patients with gout and correlated with the clinical markers of inflammation. Our findings suggest that IL-36α may be a novel inflammatory indicator for gout.

Correlations of IL-1 and IL-6 Gene polymorphisms with hypertrophic cardiomyopathy.

The purpose of this study was to explore the correlations of interleukin-1 (IL-1) and IL-6 gene polymorphisms with hypertrophic cardiomyopathy (HCM). A total of 200 patients with HCM were enrolled as disease group, and 200 healthy individuals were included as control group. Peripheral blood was collected from all subjects in both disease and control groups. Gene polymorphisms and serum expression levels of IL-1 and IL-6 were detected, and conjoint analysis was performed based on results of cardiac color Doppler ultrasound examination. The allele distribution of IL-1 rs1878320 showed a difference between disease and control groups (P=0.000). The frequency of the allele T was lower in disease group. The genotype distribution of IL-1 rs1878320 (P=0.001) and IL-6 rs1474347 (P=0.000) in disease group was different from that in control. The frequency of TC genotype of IL-1 rs1878320 was lower in disease group, and that of CA genotype of IL-6 rs1474347 was higher in disease group. There was a difference in the distribution of the dominant model of IL-6 rs1474347 between disease and control groups (P=0.021), and the frequency of CC + CA in the dominant model was 171 (0.855). The frequency of AC haplotype of IL-1 gene was overtly higher in disease group (P=0.000), while the frequency of AT haplotype was lower in disease group (P=0.000). The IL-1 rs1516792 polymorphism had an association with serum IL-1 level (P<0.05), the IL-1 level was notably increased in the patients with the genotype AA, and it was higher in disease group. The polymorphism of rs1878320 locus in IL-1 gene was correlated with interventricular septal (IVS) (P=0.047), and IVS was reduced in the patients with TC genotype. The polymorphism of rs1516792 locus in IL-1 gene was distinctly related to left ventricular outflow tract (LVOT) (P=0.041), and LVOT was lowered in the patients with GG genotype. The IL-6 rs2069831 polymorphism was associated with left ventricular ejection fraction (LVEF) (P=0.035), and LVEF declined in the patients with TT genotype. The IL-1 and IL-6 gene polymorphisms are correlated with the susceptibility and progression of HCM.

Interleukin 41 As A Potential Predictor of Bio-Therapy Efficacy In Patients With Rheumatoid Arthritis: A Prospective Observational Study.

Introduction: A novel immunomodulatory cytokine IL-41 is associated with the pathogenesis of Graves disease, Kawasaki disease, gout, psoriatic arthritis, and rheumatoid arthritis (RA). We aimed to evaluate serum IL-41 level as a biomarker of the RA and disease activity treatment efficacy and patient responses. We also wanted to determine eventual potential predictors of IL-41 concentrations. Methods and analysis: This observational clinical trial will enrol 189 patients rheumatology clinics of the Clinical Center Kragujevac, Serbia. Participants will be divided into three groups: patients on methotrexate monotherapy (MTX), (n=31), those treated with combined therapy of MTX plus TNF inhibitors (TNFi) (n=70), and patients treated with monotherapy with IL-6 inhibitor tocilizumab (TCZ) (n=43). Newly diagnosed RA or patients who for some reason were excluded from the DMARDs for a minimum of 3 months were considered as the control group (n=45). Results: TCZ reduced the IL-41 level the most. All treatment options significantly reduced clinical signs, symptoms and the scores of disease activity composite indices, TCZ the most. The only statistically significant predictor of higher IL-41 values was smoking. Conclusion: IL-41 may be a new potential biomarker that can help physicians evaluate treatment efficacy and predict patient responses. Smoking status is associated with the higher concentration of IL- 41 and clinical presentation of patients with RA.

Serum Levels of Interleukins in Endometriosis Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: The aims of this systematic review and meta-analysis were to produce a comprehensive survey of the serum levels of interleukins (ILs) in untreated people with endometriosis compared with people without endometriosis. DATA SOURCES: A systematic literature search of English language studies within Cinahl, Medline Complete, PubMed, and Scopus from inception to May 2023 was performed. METHODS OF STUDY SELECTION: We included studies that compared IL serum levels in people with endometriosis to those without endometriosis. Meta-analysis was performed on IL-1RA, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-37. TABULATION, INTEGRATION, AND RESULTS: The systematic search retrieved 651 studies, of which 77 underwent a full-text review. A total of 30 studies met inclusion criteria for the meta-analysis. IL-1Ra, IL-6, and IL-37 serum levels were 2.56 (95% CI 2.20-2.92, p <.001), 1.38 (95% CI 0.58-2.17, p <.001), and 1.77 (95% CI 1.33-2.20, p <.001) standard deviations higher in the patients with endometriosis compared with patients without endometriosis while IL-23 serum levels 0.40 (95% CI -0.73 to -0.07, p = .02) standard deviations lower, respectively. CONCLUSION: There is mounting evidence that ILs, especially IL-6, may be good candidates for unique noninvasive diagnostic tools and/or treatment pathways for endometriosis.

Association of interleukin-1 and interleukin-6 levels in lateralized temporal epilepsy patients.

Objectives: To explore the clinical significance of interleukin-1 and interleukin-6 in the development of lateralized temporal epilepsy. METHODS: The prospective study was conducted from January to April of 2022 at the Neurology Department of Training and Research Hospital, Istanbul Medeniyet University, Turkey, and comprised patients with lateralized temporal epilepsy aged 18-86 years who were in the interictal period in group A and healthy controls in group B. The levels of interleukin-1 and interleukin-6 of patients in both groups were compared. Data was analysed using SPSS 25. RESULTS: Of the 92 subjects, 60(65.2%) were in group A; 35(58.3%) were males and 25(41.7%) were females with a median age of 37.5 years (interquartile range: 2.2-42.7 years). There were 32(34.8%) subjects in group B; 19(40.6%) females and 13(40.6%) males with a median age of 40.5 years (interquartile range: 25-50 years) (p>0.05). Within group A, 41(68.3%) patients had left-sided epilepsy and 19(31.7%) had right-sided epilepsy (p<0.001). Both interleukin-1 and interleukin-6 levels were lower in group A than in group B (p<0.001). Both interleukin levels did not significantly differ between right and leftlateralised temporal seizures (p=0.44). In the left-lateralized temporal seizures, interleukin-1 levels correlated with epilepsy duration (p<0.006), lower onset age (p<0.050), and presence of prenatal risk (p<0.028). Interleukin-1 and interleukin-6 levels were positively correlated with each other for lateralized temporal epileptic hemispheres (p<0.001). CONCLUSIONS: Interleukin-1 level was correlated with epilepsy duration, lower onset age, and presence of prenatal risk in the left-lateralized temporal epilepsy.

Serum interleukin-1 is a new biomarker to predict the risk of rebleeding of ruptured intracranial aneurysm after admission.

Interleukin-1 (IL-1) could induce inflammation of the aneurysm wall, which might be related to intracranial aneurysm rupture. The aim of this study was to investigate whether IL-1 could serve as a biomarker to predict the risk of rebleeding after admission. Data between January 2018 and September 2020 were collected from patients with ruptured intracranial aneurysms (RIAs) and were retrospectively reviewed. The serum IL-1ß and IL-1ra levels were detected using a panel, and IL-1 ratio was calculated as the log10 (IL-1ra/IL-1ß). The predictive accuracy of IL-1 compared with previous clinical morphology (CM) model and other risk factors were evaluated by the c-statistic. Five hundred thirty-eight patients were finally included in the study, with 86 rebleeding RIAs. The multivariate Cox analysis confirmed aspect ratio (AR) > 1.6 (hazard ratio (HR), 4.89 [95%CI, 2.76-8.64], P < 0.001), size ratio (SR) > 3.0 (HR, 2.40 [95%CI, 1.34-4.29], P = 0.003), higher serum IL-1ß (HR, 1.88 [95%CI, 1.27-2.78], P = 0.002), and lower serum IL-1ra (HR, 0.67 [95%CI, 0.56-0.79], P < 0.001) as the independent risk factors for rebleeding after admission. According to the c-statistics, the IL-1 ratio had the highest predictive accuracy (0.82), followed by IL-1ra and IL-1ß (0.80), AR > 1.6 (0.79), IL-1ra (0.78), IL-1ß (0.74), and SR > 3.0 (0.56), respectively. Subgroup analysis based on AR and SR presented similar results. The model combining IL-1 ratio and CM model showed higher predictive accuracy for the rebleeding after admission (c-statistic, 0.90). Serum IL-1, especially IL-1 ratio, could serve as a biomarker to predict the risk of rebleeding after admission.

Analysis of serum cytokine and protective vitamin D levels in severe cases of COVID-19.

In this study, we investigated the role and relationship between the cytokine profile and protective vitamin D by measuring their serum levels in COVID-19 intensive care unit patients with severe illnesses. A total of 74 patients were included in our study. Patients were divided into two groups. Patients in the COVID-19 group (n = 31) and individuals without a history of serious illness or infection were used as the control group (n = 43). The serum concentrations of interleukin-1 (IL-1), IL-6, IL-10, IL-21, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assays. Levels of serum vitamin D were detected with Liquid chromatography-mass spectrometry methodologies. TNF-α, IL-1, IL-6, IL-10, IL-21, and vitamin D levels were measured in all patients. The serum cytokine levels in the COVID-19 patient group were significantly higher (151.59 ± 56.50, 140.37 ± 64.32, 249.02 ± 62.84, 129.04 ± 31.64, and 123.58 ± 24.49, respectively) than control groups. Serum vitamin D was also significantly low (6.82 ± 3.29) in patients in the COVID-19 group than the controls (21.96 ± 5.39). Regarding the correlation of vitamin D with cytokine levels, it was significantly variable. Our study shows that COVID-19 patients are associated with lower serum vitamin D and higher pro-inflammatory cytokines associated with increased virus presence. Our data provide more evidence of the anti-inflammatory effect of vitamin D on COVID-19 patients and the protective effects of vitamin D on risk were demonstrated.

Interleukin-36α is elevated in diffuse systemic sclerosis and may potentiate fibrosis.

Systemic sclerosis (SSc) is an autoimmune prototypical connective tissues disease that results in alterations in vasculature, inflammation and fibrosis of the skin. Interleukin-1 family cytokines has been implicated in the disease including IL-1. IL-36α is an IL-1 family member that is clearly implicated in psoriatic skin disease but its role in systemic sclerosis disease is not clear. The aim of this work is to evaluate the levels and role of IL-36α in systemic sclerosis. Early diffuse SSc patients sera was isolated along with healthy controls and IL-36 levels quantified by ELISA. In vitro analysis was also undertaken with primary dermal fibroblasts with recombinant IL-36α and keratinocyte cells were also incubated with IL-36α. Cytokines were measured by ELISA. Serum IL-36 was significantly elevated compared to healthy controls. Elevated neutrophil elastase was also elevated in the matched sera. IL-36 was not directly pro-fibrotic in dermal fibroblasts but did induce pro-inflammatory cytokines that were dependant on the MAPK pathway for their release. IL-36α also led to release of CCL20 and CCL2 in keratinocytes which may potentiate fibrosis. IL-36α is elevated in SSc serum and whilst not directly pro-fibrotic it may through keratinocytes, potentiate fibrosis through keratinocyte-immune fibroblast cross-talk.

IL-35 and IL-37 are negatively correlated with high IgE production among children with asthma in Saudi Arabia.

BACKGROUND: Asthma is one of the most prevalent inflammatory disorders among children in Saudi Arabia. OBJECTIVE: This study aimed to determine the correlation between the serum levels of vitamin D, immunoglobulin E (IgE), and cytokine (interferon-gamma (IFN-γ), interleukin (IL)-1ß, IL-4, IL-6, IL-10, IL-13, IL-35, and IL-37) in relation to the severity of disease in patients with asthma. METHODS: This case-control study was carried out at King Abdullah Specialist Children's Hospital, Saudi Arabia, and included 48 patients with asthma and 47 matched controls, aged 6-14 years. A validated questionnaire was administered to the participants, after which each patient with asthma underwent pulmonary function tests. The serum levels of vitamin D, IgE, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-35, and IL-37 of each participant were also measured. RESULTS: Patients with asthma demonstrated significantly higher IgE and cytokine (IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-35, and IL-37) levels compared to the control group (p value < .001). The levels of IL-1ß, IL-4, IL-10, and IL-13 were consistently positively correlated with the serum levels of IgE among patients with asthma. However, the IgE levels in patients with asthma were consistently negatively correlated with IL-35 and IL-37. CONCLUSIONS: We found significantly higher levels of eosinophils, IgE, IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-35, and IL-37 in patients with asthma compared to the controls, but no relationship between vitamin D and asthma.

Correlation Between Early Plasma Interleukin 37 Responses With Low Inflammatory Cytokine Levels and Benign Clinical Outcomes in Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: The immune protective mechanisms during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection remain to be deciphered for the development of an effective intervention approach. METHODS: We examined early responses of interleukin 37 (IL-37), a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients before any clinical intervention and determined its correlation with clinical prognosis. RESULTS: Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses were correlated with earlier viral RNA negative conversion, chest computed tomographic improvement, and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower interleukin 6 and interleukin 8 (IL-8) and higher interferon α responses and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and C-reactive protein. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2-transgenic mice infected with SARS-CoV-2. CONCLUSIONS: Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I interferon, thereby maintaining the functionalities of vital organs. IL-37, IL-8, and C-reactive protein might be formulated as a precise prediction model for screening severe clinical cases and have good value in clinical practice.

Elevated interleukin-37 associated with tophus and pro-inflammatory mediators in Chinese gout patients.

INTRODUCTION: Interleukin-37(IL-37), a natural inhibitor of innate immunity, has been identified to protect against various inflammatory diseases, including monosodium urate (MSU)-induced inflammation. However, the association of IL-37 with clinical indexes and pro-inflammatory mediators in gout patients remains unclear. The aim of this study was to determine IL-37 level in hyperuricemia and gout patients with or without tophus, and to investigate the correlations of IL-37 with clinical indexs such as Uric Acid (UA), CRP(C-reactive protein), Creatinine Clearance Rate (Ccr), Erythrocyte Sedimentation Rate (ESR) and so on, as well as with the pro-inflammatory mediators in serum including Interleukin-1ß(IL-1ß), Interleukin-6(IL-6) and Interleukin-18(IL-18) from gout patients. METHODOLOGY: The serum levels of IL-37, IL-1ß, IL-6 and IL-18 levels in serum of gout patients were determined by ELISA; the correlations between IL-37 and clinical values or pro-inflammatory mediators in serum of gout were analyzed by Spearman correlation test. RESULTS: The serum levels of IL-37 were higher in active gout patients than inactive gout patients and HCs, especially in active gout patients with tophus. No significant difference was observed in serum IL-37 levels between hyperuricemia and normal controls. IL-1ß, IL-6 and IL-18 levels were significant elevated in gout patients with tophus than those without tophus; Serum IL-37 were positively correlated with CRP and ESR, as well as with IL-1ß, IL-6 and IL-18, negatively correlated with Ccr, and not correlated with UA, creatinine (Cr) and triglyceride (TG) in gout patients. CONCLUSIONS: IL-37 increased in gout patients positively associated CRP and ESR, as well as with proinflammatory mediators IL-1ß, IL-6, IL-18, the presence of tophus and chronic kidney disease in gout. It may be a novel marker for predicting this pathology.

Interleukin-37 is down-regulated in serum of patients with severe coronavirus disease 2019 (COVID-19).

Pro-inflammatory and anti-inflammatory cytokines are indicated to play a prominent role in mediating the immunopathogenesis of coronavirus disease 19 (COVID-19). Interleukin (IL-37) is one of the anti-inflammatory cytokines that has been proposed to be involved in disease progression but the data are not overwhelming. Therefore, a case-control study was performed to analyze IL-37 levels in serum of 100 patients with severe COVID-19 and 100 blood donors (control group). Median age was significantly higher in COVID-19 cases than in controls. Stratification by gender, body mass index and ABO and Rh blood group systems showed no significant differences between patients and controls. Chronic diseases (cardiovascular and diabetes) were observed in 57.0% of patients. Serum levels of IL-37 and vitamin D were significantly decreased in patients compared to controls. The low level of IL-37 was more pronounced in males, overweight/obese cases, blood group B or AB cases, Rh-positive cases, and cases with no chronic disease. Low producers of IL-37 were more likely to develop COVID-19 (odds ratio = 2.66; 95% confidence interval = 1.51-4.70; corrected probability = 0.015). Receiver operating characteristic curve analysis demonstrated that a low serum level of IL-37 was a good predictor of COVID-19. Spearman's rank correlation analysis showed that IL-37 and vitamin D were significantly correlated. In conclusion, IL-37 was down-regulated in serum of patients with severe COVID-19 compared to controls. This down-regulation may be associated with an increased risk of disease. Gender, body mass index, blood groups and chronic disease status may also affect IL-37 levels.

Effects of intravenous lidocaine, dexmedetomidine, and their combination on IL-1, IL-6 and TNF-α in patients undergoing laparoscopic hysterectomy: a prospective, randomized controlled trial.

BACKGROUND: Surgical-related inflammatory responses have negative effects on postoperative recovery. Intravenous (IV) lidocaine and dexmedetomidine inhibits the inflammatory response. We investigated whether the co-administration of lidocaine and dexmedetomidine could further alleviate inflammatory responses compared with lidocaine or dexmedetomidine alone during laparoscopic hysterectomy. METHODS: A total of 160 patients were randomly allocated into four groups following laparoscopic hysterectomy: the control group (group C) received normal saline, the lidocaine group (group L) received lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion), the dexmedetomidine group (group D) received dexmedetomidine (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion), and the lidocaine plus dexmedetomidine group (group LD) received a combination of lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion) and dexmedetomidine (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion). The levels of plasma interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at different time points were the primary outcomes. Secondary outcomes included hemodynamic variables, postoperative visual analogue scale (VAS) scores, time to first flatus, and incidence of nausea and vomiting after surgery. RESULTS: The levels of plasma IL-1, IL-6, and TNF-α were lower in groups D and LD than in group C and were lowest in group LD at the end of the procedure and 2 h after the operation (P < 0.05). The VAS scores were decreased in groups D and LD compared with group C (P < 0.05). The heart rate (HR) was decreased at the end of the procedure and 2 h after the operation in groups D and LD compared to groups C and L (P < 0.001). The mean blood pressure (MBP) was lower at 2 h after the operation in groups L, D, and LD than in group C (P < 0.001). There was a lower incidence of postoperative nausea and vomiting (PONV) in group LD than in group C (P < 0.05). CONCLUSIONS: The combination of lidocaine and dexmedetomidine significantly alleviated the inflammatory responses, decreased postoperative pain, and led to fewer PONV in patients undergoing laparoscopic hysterectomy. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03276533 ), registered on August 23, 2017.

Elevated levels of interleukin-35 and interleukin-37 in adult patients with obstructive sleep apnea.

BACKGROUND: Systemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)-35 and IL-37 have been identified as novel immune-modulating cytokines with anti-inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL-35 and IL-37 in patients with OSA, and to investigate their associations with the severity of OSA. METHODS: A total of 97 patients, including 67 cases of OSA and 30 age- and gender-matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL-35, IL-37, and pro-inflammatory cytokine IL-1ß levels were examined by ELISA. RESULTS: Compared with those in the control subjects, serum IL-35, IL-37, and IL-1ß levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity-dependent increase in serum IL-35 and IL-37 levels was observed in patients with OSA. IL-35 and IL-37 levels were positively correlated with the apnea-hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = -0.461 and -0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = -0.616 and -0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL-35 or IL-37 and IL-1ß levels (all p < 0.001). CONCLUSION: The serum levels of IL-35 and IL-37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL-35 and IL-37 may have a protective role in OSA by counteracting inflammatory responses.

Serum IL-36 cytokines levels in type 2 diabetes mellitus patients and their association with obesity, insulin resistance, and inflammation.

BACKGROUND: The interleukin (IL)-36 cytokines include IL-36α, IL-36ß, IL-36γ, and IL-36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM). METHODS: The study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high-performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL-36α, IL-36γ, IL-36Ra, and IL-17 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum IL-36α, IL-36γ, and IL-17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL-36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL-36α was positively correlated with high sensitivity C-reactive protein. Serum IL-36α was negatively correlated with IL-36Ra. Serum IL-17 was negatively correlated with low-density lipoprotein cholesterol. CONCLUSIONS: This study demonstrated that T2DM patients displayed increased IL-36α and IL-36γ expression and decreased IL-36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL-36 cytokines may be a new target for the diagnosis or treatment of T2DM.

Hsa_circ_0054633 association of C peptide is related to IL-17 and TNF-α in patients with diabetes mellitus receiving insulin treatment.

BACKGROUND: Chronic inflammation damaged the islet and resulted in dysfunction of T2D. Circular RNA is stable and better for biomarker in many diseases. Here, we aimed to identify potential circular RNA hsa_circ_0054633 that can be a biomarkers for the effects of insulin therapy in T2D. METHODS: In this retrospective case-control study, patients were from Li Huili Hospital, Ningbo, China, from February 10, 2019, to August 15, 2019. We included 47 healthy adults, 46 new-onset T2D with insulin resistance, and 51 patients with insulin therapy. Serum inflammation factors were tested by ELISA assays. We selected hsa_circ_0054633 as a candidate biomarker and measured its concentration in serum by qRT-PCR. The Pearson correlation test was used to evaluate the correlation between this circRNA and clinical variables. RESULTS: Clinical data indicated that serum C peptide was increased in T2D treatment with insulin. Serum hsa_circ_0054633 was decreased in insulin treatment group. Hsa_circ_0054633 was negative correlated with C peptide (r = -0.2841, p = 0.0433,). IL-1 and IL-6, IL-17, and TNF-α were higher in T2D patients and decreased after insulin treatment, only IL-17 and TNF-α showed a positive correlation to hsa_circ_0054633 (r = 0.4825, p < 0.0001, and r = 0.6190, p < 0.0001). The area under ROC curve was 0.7432, 0.5839, and 0.7573 for Hsa_circ_0054633, C peptide, and their combination. CONCLUSION: Hsa_circ_0054633 level was lower in T2D with insulin treatment than untreated and was a negative correlation with C peptide, and positively correlated with IL-17 and TNF-α, suggesting that hsa_circ_0054633 may be a potential early indicator of insulin treatment effect to improve inflammation condition.

IL-38: A novel cytokine in systemic lupus erythematosus pathogenesis.

IL-38 is a newly identified cytokine that belongs to the IL-1 family. In our previous study, we found elevated plasma levels of IL-38 in patients with systemic lupus erythematosus (SLE). However, the clear relationship of IL-38 expression in plasma, peripheral blood mononuclear cells (PBMCs) and clinical and laboratory features needs elucidation. Additionally, we evaluated the possible role of IL-38 in regulating production of inflammatory cytokines in PBMCs in vitro. A pristane-induced murine lupus model was used to further demonstrate the effects of IL-38 on cytokines in vivo and discuss the significance of IL-38 in lupus development. The results showed that mRNA expression of IL-38 in PBMCs of patients with SLE was elevated compared with volunteers, and expression of IL-38 in both plasma and PBMCs was strongly related to clinical features, such as haematuria and proteinuria, and correlated with a SLEDAI score. Plasma levels of TNF-α, IL-1ß, IL-6 and IL-23 were elevated in patients with SLE and were related to plasma levels of IL-38. In vitro, PBMCs of patients with SLE stimulated with IL-38 showed a decreased expression of the four inflammatory cytokines compared with PBMCs of patients without treatment. Interestingly, IL-38 administration in lupus mice significantly reduced the development of lupus, such as reduced proteinuria, improved histological examinations of the kidneys and down-regulated inflammatory cytokines. In conclusion, IL-38 may suppress synthesis of pro-inflammatory cytokines and therefore regulate lupus pathogenesis.