Effect of Perineural or Intravenous Betamethasone on Femoral Nerve Block Outcomes in Knee Arthroplasty: A Randomized, Controlled Study.

OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.

Maternal serum interleukin-1ß, FoxO1 and Sestrin2 levels in predicting preterm delivery.

The study aimed to investigate whether serum IL-1ß, FoxO1and Sesn2 concentrations differed between threatened preterm labor (TPL) and uncomplicated pregnancies. This study was conducted on 54 women with TPL pregnancies and 26 healthy pregnant women. The TPL group was further divided into two subgroups according to the gestational age at delivery. Patients who gave birth within 48-72 hours after the hospitalization were referred to as preterm delivery (PD) and those who gave birth at ≥37 weeks were referred to as term delivery (TD). Maternal levels of serum IL-1ß, FoxO1 and Sesn2 were measured with the use of enzyme-linked immunosorbent assay kits. The mean maternal serum IL-1ß and FoxO1 of PD were significantly higher than TD (p<.000*) and the control group (p < .000*). The mean maternal serum IL-1ß, FoxO1 level of TD was significantly higher than the control group (p<.000*). The mean maternal serum Sesn2 levels of TD and the control group were significantly higher than the preterm group (p<.000*). The mean maternal serum Sesn2 level of the control group was significantly higher than the TD group (p <.000*). A negative correlation was found between serum concentration of serum IL-1ß, and FoxO1 with the gestational week of delivery (r= -0.722, p< .000*for, IL-1ß; r = -0.625, p < .000* for FoxO1). A positive correlation was found between the serum concentration of serum Sesn2 with the gestational week of delivery (r = 0.507, p<.000* for sesn2). High serum IL-1ß, FoxO1 levels, and low Sesn2 levels may have the potential to be used as biomarkers for the differentiation of PD and TD.

Elevated IL-1ß and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players.

Autologous platelet-rich plasma (PRP) therapy has been becoming popular for the treatment of musculotendinous injuries among athletes. However, for individual and practical variations, clinical success is hardly predictable. To overcome this difficulty, we have been exploring possible criterion candidates for monitoring its clinical effectiveness. In this study, we focused on sex-based differences in young elite athletes and compared the biochemical compositions of their PRP. Leukocyte-rich PRP (L-PRP) was manually prepared from blood samples collected from male professional soccer players (mPSPs) (n = 25) and female college athletes (fCAs) (n = 36). Platelet-derived growth factor-BB (PDGF-BB), transforming-growth factor-ß1 (TGFß1), platelet factor-4 (PF4), interleukin-1ß (IL-1ß), and IL-1 receptor antagonist (IL-1RA) were quantified using an enzyme-linked immunosorbent assay. The levels of PDGF-BB, TGFß1, and PF4 in L-PRP were significantly higher in mPSPs than in fCAs. Conversely, IL-1ß and IL-1RA were detected at significantly and slightly higher levels, respectively, in fCAs than in mPSPs. Our findings suggest that, even though L-PRP from fCAs may have lower potential to induce cell growth and differentiation than that of mPSPs, due to the latter's higher capacity to control inflammation, it does not necessarily imply that PRP treatment in fCAs is less effective. Thus, these cytokine levels should be checked before PRP therapy.

Evaluation of the relationship between serum interleukin-1ß levels and expression of inflammasome-related genes in patients with COVID-19.

BACKGROUND: Inflammasomes are a group of molecules that are strongly involved in causing inflammation. This study aimed to evaluate the expression of NLR family pyrin domain containing 1 (NLRP1), NLRP3, and Apoptosis-associated speck-like protein containing a CARD (ASC) as well as their association with serum level of interleukin (IL)-1ß in patients with coronavirus disease 2019 (COVID-19). METHODS: Thirty COVID-19 patients and 30 healthy subjects (HS) were recruited. Peripheral blood specimens were collected from subjects to assess NLRP1, NLRP3, and ASC gene expression by Real time-PCR technique. Serum levels of IL-1ß were also measured via the enzyme-linked immunosorbent assay (ELISA). RESULTS: The findings showed no significant differences in serum IL-1ß level between COVID-19 patients and the HS group. mRNA expression of ASC (P = 0.008) and NLRP1 (P = 0.03) gene had a significant increase in COVID-19 patients compared to HS, while there was no significant increase in the expression of NLRP3 between the studied group. There were significant correlations between patient's data and expression levels of NLRP1, NLRP3, IL-1ß, and ACS. CONCLUSIONS: NLRP1 and ASC may have a more critical role in the generation of the active form of IL-1ß in COVID-19 patients compared to NLRP3. However, serum levels of IL-1ß in patients did not show a significant increase, which may be due to the patient's condition and the application of virus escape mechanisms through impaired NLRP3 expression and its malfunction.

The high level of IL-1ß in the serum of ACLF patients induces increased IL-8 expression in hUC-MSCs and reduces the efficacy of hUC-MSCs in liver failure.

BACKGROUND: Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients' serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs. METHODS: The serum of surviving and dead ACLF patients was collected to culture hUC-MSCs in vitro, and the hUC-MSCs cultured in the serum of ACLF patients were used to treat acute liver failure (ALF) rats. The therapeutic effect on the rats was evaluated by a survival curve, the transaminase level and liver histopathology. The expression of cytokines in hUC-MSCs was detected by Q-PCR and ELISA. RESULTS: Serum pretreatment reduced the therapeutic effect of hUC-MSCs on ALF, especially pretreatment in the serum from dead ACLF patients. After hUC-MSCs were cultured in the serum of surviving or dead ACLF patients, the most differentially expressed factor was IL-8. Interfering with the expression of IL-8 in hUC-MSCs can improve the therapeutic effect of hUC-MSCs on ALF. The high level of IL-1ß in the serum of dead ACLF patients causes the increased expression of IL-8 in hUC-MSCs through the activation of the NF-κB signaling pathway. Meanwhile, we found that the neutralizing IL-1ß in serum from dead ACLF patients can improve the therapeutic effect of hUC-MSCs on ALF. CONCLUSION: The high level of IL-1ß in ACLF serum can promote the expression of IL-8 in hUC-MSCs through the NF-κB signaling pathway, thus reducing the effect of hUC-MSCs on ALF.

IL-17A/p38 Signaling Pathway Induces Alveolar Epithelial Cell Pyroptosis and Hyperpermeability in Sepsis-Induced Acute Lung Injury by Activating NLRP3 Inflammasome.

Sepsis is a syndrome with poor prognosis. Nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and T helper 17 (Th17) cells are involved in the pathogenesis of inflammatory diseases. This study aims to explore their roles and underlying mechanisms in sepsis. The blood and bronchoalveolar lavage fluid are collected from sepsis patients and healthy donors. A sepsis mice model is established by cecal ligation puncture (CLP). The contents of cytokines are detected by ELISA. The amounts of Th17 cells, IL-17A, IL-1ß, IL-18, and lipopolysaccharide is significantly elevated in sepsis patients. The increased differentiation of Th17 cells can promote lung cell pyroptosis and induce hyperpermeability via activating NLRP3 inflammasome and p38 pathway. The inhibitors targeting Th17 cells, NLRP3 inflammasome, and p38 pathway can significantly alleviate lung injury in sepsis mice. Th17 cells can secrete IL-17A to activate NLRP3 inflammasome via p38 signaling pathway, which contributes to the development of sepsis-induced acute lung injury.

Increased Serum Levels of IL-1ß after Ischemic Stroke are Inversely Associated with Vitamin D.

Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1ß (IL-1ß) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders. Objective: To investigate the levels of IL-1ß and vitamin D (VitD) in patients with IS compared with controls and their correlation. Methods: The serum level of 25-OH VitD and IL-1ß was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit. Results: We found a significant increase in IL-1ß (80.14±6.8 vs. 60.32±4.1 pg/ml, p<0.05) and a decrease in VitD level (24.3±1.4 vs. 29.9±1.5 ng/ml, p<0.01) in the IS patients compared with the controls. There was a significantly positive correlation between the National Institutes of Health Stroke Scale (NIHSS) and IL-1ß according to both the Spearman correlation (r=0.35, p=0.0003) and the linear regression (beta=0.255, p=0.014). Also, a significant negative association between VitD and NIHSS was detected by the Spearman correlation (r=-0.41, p<0.0001) and the linear regression (beta=-0.381, p=0.000). Moreover, we found a significant negative correlation (r=-0.26, p=0.006) between the serum levels of VitD and IL-1ß in the patient group. Conclusion: Ischemic stroke correlates positively with IL-1ß and negatively with VitD levels. The speculated role of VitD deficiency in the evolution and severity of stroke may be justified by its role in the modification of inflammation.

Value of IL-1ß and IL-23 in Predicting 28-Day Mortality Due to Sepsis: A Retrospective Study.

BACKGROUND This research aimed to explore the utility of Interleukin-1ß (IL-1ß) and IL-23 as potential biomarkers for the diagnosis and prognosis of sepsis. MATERIAL AND METHODS This study included 74 adult individuals with sepsis, 45 ICU controls, and 50 healthy individuals attending routine physical examinations. IL-1ß and IL-23 levels were assessed and analyzed on the admission day. Univariate Cox regression analyses were utilized to explore the association of IL-1ß and IL-23 with sepsis survival. Furthermore, receiver operating characteristic (ROC) analysis was employed to evaluate the value of IL-1ß and IL-23 to predict 28-day mortality due to sepsis. RESULTS Serum concentrations of IL-1ß and IL-23 were significantly higher in septic patients relative to healthy and ICU controls (P<0.001). IL-1ß and IL-23 levels in non-survivors were significantly higher than in survivors (P<0.001). IL-1ß (hazard ratio; HR=1.06, P<0.001) and IL-23 (HR=1.02, P=0.031) were independent risk variables for 28-day mortality in sepsis patients, which were strongly associated with the severity of sepsis. The area under the ROC curve for predicting 28-day fatality in sepsis was 0.66 for IL-1ß (P=0.024, 95% confidence interval; CI: 0.54-0.76) and 0.77 for IL-23 (P<0.001, 95% CI: 0.65-0.86). Furthermore, compared with low serum IL-1ß (<9.41 pg/mL) and IL-23 (<6.77 pg/mL) levels, septic patients with high serum IL-1ß (≥9.41 pg/mL) and IL-23 (≥6.77 pg/mL) levels had poorer survival. CONCLUSIONS Serum IL-1ß and IL-23 values were higher in patients with sepsis and are potential diagnostic and prognostic markers for sepsis, but this needs to be confirmed by prospective studies.

Serum Cu, Zn and IL-1ß Levels May Predict Fetal Miscarriage Risk After IVF Cycles: A Nested Case-Control Study.

To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nested case-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1ß and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1ß, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1ß, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion, the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1ß and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1ß, Cu and Zn might synergistically predict pregnancy outcome.

Evaluation of the association between circulating IL-1ß and other inflammatory cytokines and incident atrial fibrillation in a cohort of postmenopausal women.

BACKGROUND: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1ß, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. METHODS: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease. RESULTS: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1ß log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log [pg/mL] increase, P= .24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-α. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF. CONCLUSIONS: In this large cohort of postmenopausal women, there was no significant association between IL-1ß and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF.

Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is a prevalent articular disease mainly characterized by extracellular matrix degradation, apoptosis, and inflammation, which lead to cartilage destruction and abnormal bone metabolism. With undesirable side effects, current limited symptomatic treatments are aimed at relieving pain and improving joint mobility in patients with OA. Intra-articular (IA) hyaluronic acid (HA) injection, as a nonsurgical therapy, is commonly used in the clinical management of knee OA, but the efficacy of this therapeutic option remains controversial. Ebselen has tremendous pharmacological importance for some diseases due to its antioxidant, antiapoptotic, and anti-inflammatory features. However, there is no research examining the therapeutic effect of Ebselen in OA using the rat OA model. Therefore, we aimed to investigate the therapeutic effect of Ebselen on cartilage degeneration and its role in bone morphogenetic protein 2 (BMP2) and nuclear factor kappa B (NF-κB) signaling in the molecular pathogenesis of OA. We induced a knee OA model in rats with an IA injection of monosodium-iodoacetate (MIA). After the treatment of Ebselen, we evaluated its chondroprotective effects by morphological, histopathological, and immunohistochemical methods and an enzyme-linked immunosorbent assay. We report for the first time that Ebselen treatment alleviated articular cartilage degeneration in the rat knee OA model and reduced MIA-induced BMP2 and NF-κB expressions. In addition, our results unveiled that Ebselen decreased IL-ß and IL-6 levels but did not affect COMP levels in the rat serum. Ebselen could be a promising therapeutic drug for the prevention and treatment of OA by alleviating cartilage degeneration and regulating BMP2 and NF-κB expressions.

Serum IL-1ß predicts de novo hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C, not during anti-cancer/immunosuppressive therapy.

De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1ß levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94-333.3). HCV-infected patients with the IL-1ß gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1ß levels; no HCV-infected patient with the IL-1ß AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1ß levels. Low IL-1ß levels were not associated with HBV reactivation. IL-1ß levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.

Serum interleukin 1ß in patients with acquired laryngotracheal stenosis.

Objectives: To determine the serum levels of interleukin-1beta (IL-1ß) in patients with acquired laryngotracheal stenosis (ALTS) and healthy volunteers and compare levels between serum and tissue of the stenotic segment. Materials and methods: An exploratory cohort study included 20 participants with ALTS and 5 healthy volunteers. ALTS group was categorised into mild and severe according to grade of stenosis and presence of tracheostomy. Comparisons of serum levels of IL-1ß between pre- and post-surgical intervention and between blood and tissue samples in the severe ALTS group were made. Correlation of IL-1ß levels between blood and tissue was assessed using Spearman's correlation. Results: Severe ALTS patients showed higher serum levels of IL-1ß compared to mild ALTS and healthy volunteers (p = 0.045). IL-1ß was higher before surgical intervention than after surgical intervention (p = 0.003). There was a strong positive correlation of IL-1ß between serum and tissue (r = 0.74, p = 0.035). Conclusion: Serum levels of IL-1ß are higher in ALTS patients than in healthy controls and positively correlate with tissue levels. The decreasing trend of serum IL-1ß observed following successful surgical intervention reflects the absence of ongoing inflammation at the stenotic segment.

Correlation of Serum IL-18, BDNF, and IL-1ß with Depression and Prognosis after Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective: To explore the correlation of serum IL-18, BDNF, and IL-1ß with depression and prognosis after acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods: By means of retrospective analysis, the data of 240 patients at the acute exacerbation of COPD treated in our hospital (February 2018-February 2021) were analyzed. All patients received conventional treatment 1 d after admission, patients' serological indicators were measured before treatment, and after 30 d of follow-up, the patients were divided into the survival group (SG) and death group (DG) according to their clinical outcomes, the Beck's Depression Inventory (BDI) scores of the surviving patients were investigated, the correlation of IL-18, BDNF, and IL-1ß levels with depression was analyzed by R analytics, and the correlation of IL-18, BDNF, and IL-1ß levels with prognosis was analyzed by ROC curve analysis. Results: The results of 30 d follow-up showed that 220 patients survived (91.7%) and 20 patients died (8.3%). Among the surviving patients, 95 patients had depression and 125 patients did not have depression; the BDI scores of the depressed subjects and the nondepressed subjects were 10.35 ± 1.25 points and 2.06 ± 0.76 points, respectively; significant differences in IL-18, BDNF, and IL-1ß levels between SG and DG were observed (P < 0.05); significant differences in IL-18, BDNF, and IL-1ß levels between the depressed subjects and the nondepressed subjects were observed (538.43 ± 19.02 vs. 515.32 ± 9.65, 7.54 ± 0.56 vs. 12.11 ± 2.41, and 8.70 ± 0.98 vs. 8.12 ± 0.87; P < 0.001); among the depressed patients, the IL-18 and IL-1ß levels were positively correlative with the BDI scores (r = 0.781, r = 0.2583, P < 0.001, P = 0.012), and the BDNF level was negatively correlative with the BDI scores (r = -0.3277, P = 0.001) before treatment; according to the ROC analysis, the AUC (95% CI) of IL-18, BDNF, and IL-1ß in predicting prognosis was 0.8770 (0.8281-0.9260), 0.7723 (0.6879-0.8567), and 0.7165 (0.6080-0.8250) (P < 0.05), respectively. Conclusion: In regard to the depression in COPD patients after acute exacerbation, IL18 and IL-1ß show positive correlation, and BDNF presents negative correlation. All three indicators have predictive value for patient outcome.

Neural circuits mediating circulating interleukin-1ß-evoked fever in the absence of prostaglandin E2 production.

Infectious diseases and inflammatory conditions recruit the immune system to mount an appropriate acute response that includes the production of cytokines. Cytokines evoke neurally-mediated responses to fight pathogens, such as the recruitment of thermoeffectors, thereby increasing body temperature and leading to fever. Studies suggest that the cytokine interleukin-1ß (IL-1ß) depends upon cyclooxygenase (COX)-mediated prostaglandin E2 production for the induction of neural mechanisms to elicit fever. However, COX inhibitors do not eliminate IL-1ß-induced fever, thus suggesting that COX-dependent and COX-independent mechanisms are recruited for increasing body temperature after peripheral administration of IL-1ß. In the present study, we aimed to build a foundation for the neural circuit(s) controlling COX-independent, inflammatory fever by determining the involvement of brain areas that are critical for controlling the sympathetic outflow to brown adipose tissue (BAT) and the cutaneous vasculature. In anesthetized rats, pretreatment with indomethacin, a non-selective COX inhibitor, did not prevent BAT thermogenesis or cutaneous vasoconstriction (CVC) induced by intravenous IL-1ß (2 µg/kg). BAT and cutaneous vasculature sympathetic premotor neurons in the rostral raphe pallidus area (rRPa) are required for IL-1ß-evoked BAT thermogenesis and CVC, with or without pretreatment with indomethacin. Additionally, activation of glutamate receptors in the dorsomedial hypothalamus (DMH) is required for COX-independent, IL-1ß-induced BAT thermogenesis. Therefore, our data suggests that COX-independent mechanisms elicit activation of neurons within the DMH and rRPa, which is sufficient to trigger and mount inflammatory fever. These data provide a foundation for elucidating the brain circuits responsible for COX-independent, IL-1ß-elicited fevers.

A cross-sectional healthy-control study of serum inflammatory biomarkers interleukin (IL)-1B and IL-2R in panic disorder patients and their offspring.

Alterations in the immune system have been associated with a variety of mental illnesses. An increase in circulating inflammatory cytokines is observed not only in people with mental disorders but also in their first-degree relatives. A considerable amount of data support the link between immune system activation and panic disorder (PD) pathogenesis, while it is still unclear whether differential immunological reactivity represents a propensity, a measure of disease activity, or both. To better understand the role of cytokines in PD pathophysiology, we compared the levels of serum inflammatory biomarkers interleukin (IL)-1B and IL-2R among PD patients, offspring of PD patients and healthy controls. The offspring of PD patients were evaluated by a psychiatrist and were considered unaffected by any mental disorder at the time of the evaluation. Concentrations of the cytokines IL-1B and IL-2R were assessed using the Immulite System (Diagnostic Products Corporation). The levels of proinflammatory markers IL-1B and IL-2R were increased in PD patients compared to those of controls, but offspring of PD patients and healthy controls demonstrated no differences regarding peripheral interleukin levels. Our findings suggest that interleukins might represent a disease-dependent marker in PD.

Chemokine (C-C motif) ligand 5 (RANTES) concentrations in the peripheral blood of patients with a depressive disorder.

BACKGROUND: Inflammation plays a role in the pathomechanism of depressive disorder. Cytokines interact with iodothyronine deiodinases (DIOs) that are involved in thyroid hormone (TH) metabolism. DIOs are known as modifiers of the inflammatory response. RANTES is a chemokine that has been detected in a wide range of inflammatory disorders, but is less studied in depression. We aimed to investigate the concentration of RANTES in patients with recurrent depressive disorder (rDD) and examine any potential correlation with other molecules, such as interleukins (ILs) and DIOs. METHODS: The levels of RANTES and other molecules associated with depressive disorder, including deiodinase type 1 (DIO1), interleukin (IL)1ß, and IL-6, were measured by enzymatic immune assay (ELISA) in the serum of 43 patients with depressive disorder and 36 controls. RESULTS: RANTES levels were higher in depressed patients than in controls. The level of RANTES was negatively correlated with the deiodinase type 1 (DIO1) level in women diagnosed with rDD. IL-1ß and IL-6 levels were significantly higher in depressed patients than in controls. IL-1ß was positively correlated with deiodinase type 3 (DIO3). A negative correlation between DIO1 and the number of depressive episodes in women with rDD was observed. CONCLUSION: With the observed elevated RANTES levels, increases in ILs concentrations, and a possible link between immune aspects and DIOa in patients with rDD, our study contributes to the current pool of knowledge about the complex aetiology of depression and suggests future studies focus on precision mechanisms that explain the link between TH-related molecules and immune molecules.

Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-κB Pathway.

Inflammatory bowel diseases (IBDs) constitute a group of chronic intestinal conditions prominently featuring deranged metabolism. Effective pharmacological treatments for IBDs are lacking. Isosteviol sodium (STV-Na) exhibits anti-inflammatory activity and may offer therapeutic benefits in chronic colitis. However, the associated mechanism remains unclear. This study is aimed at exploring the therapeutic effects of STV-Na against chronic colitis in terms of metabolic reprogramming and macrophage polarization. Results show that STV-Na attenuated weight loss and colonic pathological damage and restored the hematological and biochemical parameters in chronic colitis mice models. STV-Na also restored intestinal permeability by increasing the goblet cell numbers, which was accompanied by lowered plasma lipopolysaccharide and diamine oxidase levels. Metabolomic analysis highlighted 102 candidate biomarkers and 5 vital pathways that may be crucial in the potential pharmacological mechanism of STV-Na in regulating intestinal inflammation and oxidative stress. These pathways were glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, the pentose phosphate pathway, and phosphonate and phosphinate metabolism. Furthermore, STV-Na significantly decreased M1 macrophage polarization in the spleen and colon. The mRNA and protein levels of IL-1ß, TNF-α, and NF-κB/p65 in colonic tissue from the colitis mice were decreased after the STV-Na treatment. Overall, STV-Na could alleviate chronic colitis by suppressing oxidative stress and inflammation levels, reprogramming the metabolic profile, inhibiting macrophage polarization, and suppressing the NF-κB/p65 signaling pathway. STV-Na remains a promising candidate drug for treating IBDs.

Administration of hemin ameliorates ovarian ischemia reperfusion injury via modulation of heme oxygenase-1 and p-JNK/p-NF-κBp65/iNOS signaling pathway.

AIMS: Ovarian torsion is the fifth common gynecological emergency that can affect females of all ages particularly during reproductive age and its management by detorsion leads to ovarian ischemia reperfusion (IR) injury. Therefore, prophylactic measures are required to protect the ovarian function after detorsion. So that, our study aimed to assess the effect and underlying mechanisms of heme oxygenase-1 (HO-1) inducer; hemin against ovarian damage induced by IR injury in rats. MAIN METHODS: Female rats were divided into: sham group, hemin group, ovarian IR (OIR) groups with and without hemin treatment. Serum levels of reduced glutathione (GSH) and interleukin 1 ß (IL-1ß) were measured in addition to ovarian levels of malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD). Ovarian phospho-Janus kinase (p-JNK) levels and gene expressions of HO-1 and inducible nitric oxide synthase (iNOS) were determined. Moreover, histopathological changes and expressions of phospho-nuclear factor kappa B p65 (p-NF-κB p65) and cleaved caspase-3 were done. KEY FINDINGS: Treatment of OIR rats with hemin led to significant attenuation of ovarian damage through histological examination which was associated with significant increase in ovarian expression of HO-1, ovarian SOD and serum GSH levels with significant decrease in ovarian p-JNK levels, expressions of p-NF-κB p65, iNOS and cleaved caspase-3 in addition to serum IL-1ß levels. SIGNIFICANCE: The protective effect of hemin can be attributed to the increased expression of HO-1 which showed antioxidant, anti-inflammatory and anti-apoptotic effects. Therefore, hemin can be administered to prevent ovarian IR injury which occurs after detorsion.

Mechanical model of steady-state and inflammatory conditions in patients with relapsing polychondritis: A review.

ABSTRACT: Relapsing polychondritis (RP) is a multisystem inflammatory disorder, considered to associate with immune aberration.Increased T helper type-1 cell-related cytokines were reported in RP patients. mRNA expressions of a regulatory T cell cytokine interleukin (IL)-10 increased, whereas pro-inflammatory cytokines IL1ß and IL6 mRNA expressions decreased in freshly isolated peripheral blood mononuclear cells of RP patients compared with those in healthy individuals. Upon in vitro stimulation with mitogen, IL10 mRNA expressions decreased, and IL1ß and IL6 mRNA expressions increased in RP patients.This short-time dynamic change of gene expressions from anti-inflammatory to pro-inflammatory features of immune cells may be associated with the "relapsing" disease course of patients with RP. IL1ß mRNA expressions of peripheral blood mononuclear cells exhibited positive correlations with serum matrix metalloproteinase (MMP)-3 concentrations in patients with respiratory involvement. Such positive correlation was not found in those without respiratory involvement.In a metagenomic analysis, an altered composition of gut microbes was found, suggesting that microbe metabolites such as short-chain fatty acids may affect T cell responses of the patients.In this review, the relationships among RP-related inflammatory molecules were summarized. The data support a hypothesis that the immune conditions are different between steady-state and inflammation in RP patients.