Serum Levels Of IL-6 Research Articles

Batryticatus bombyx improved atopic dermatitis in NC/Nga mice and impact on inflammation and recovery of skin barrier via STAT1/P38/NF-κB downregulation and HO-1/Nrf2 activation in HaCaT keratinocytes.

Batryticatus bombyx (BB) (Beauveria bassiana Vuill.) is used as an herbal medicine and food additive. Although BB has neuroprotective and anti-apoptotic effects, its impacts on atopic dermatitis (AD) are unknown. We evaluated the effects of BB in an NC/Nga mouse model of house dust mite (HDM)-induced AD, in TNF-α and IFN-γ (TI)-stimulated HaCaT keratinocytes, and in a 3D human skin model. NC/Nga mice were induced with HDM and treated with BB for 6 weeks. We assessed skin symptoms, serum levels of IgE, histamine, and IL-6, immune cell counts, and performed histological analysis of dorsal skin tissue. Additionally, we induced inflammation in HaCaT cells and a 3D human skin model using TNF-α/IFN-γ. We measured inflammatory cytokine levels, skin hydration factors, and delved into underlying mechanisms via ELISA, real-time PCR, and Western blot. BB improved skin lesions, reduced thickness, and inflammatory cell infiltration in HDM-induced mice. It alleviated scratching, improved moisture retention, and reduced IgE, histamine, and IL-6 levels. In HaCaT cells, BB inhibited thymic stromal lymphopoietin and increased hyaluronan content. It also upregulated aquaporin-3, hyaluronan synthase-1/3, filaggrin, involucrin, and occludin, enhancing skin hydration and tight junction stability. BB decreased STAT1, p38 MAPK, and NF-κB p65 levels in HaCaT cells and exhibited antioxidant effects by increasing HO-1/Nrf2 expression. BB may serve as a therapeutic alternative for AD treatment by inhibiting skin inflammation.

Impact of p. Gingivalis-induced chronic apical periodontitis on systemic iron homeostasis via the hepatic IL-6/STAT3/Hepcidin signaling pathway.

Chronic apical periodontitis (CAP), an inflammatory disease of the oral cavity caused by bacterial infections with Porphyromonas gingivalis (P. gingivalis) as a key pathogen, has been associated with systemic effects, potentially influencing distant organs including liver. The liver plays a key role in iron metabolism and immunity by hepcidin. This study aims to investigate the impact of P. gingivalis-induced CAP on liver and systemic iron metabolism, focusing on the role of the IL-6/STAT3 signaling pathway in hepatic hepcidin synthesis. A murine model of CAP was established by pulp chamber infection with P. gingivalis. Serum levels of IL-6, ferritin, and hepcidin were measured via ELISA. High-throughput sequencing was used to analyze hepatic gene expression, and immunohistochemistry with fluorescent staining was performed to validate protein expression in liver tissues. CAP led to significant changes in serum iron, ferritin, and IL-6. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed enrichment in pathways like JAK/STAT signaling and acute-phase responses, and gene set enrichment analysis (GSEA) also indicated activation of IL-6/JAK/STAT3 signaling pathway. Iimmunofluorescence confirmed increased IL-6, p-STAT3, and hepcidin expression. These levels were alleviated by stattic treatment, mitigating CAP-induced inflammatory and iron-regulatory effects. P. gingivalis-induced CAP triggered systemic inflammation and disrupts iron metabolism via the IL-6/STAT3 signaling pathway, potentially affecting liver function. Targeting this pathway may offer therapeutic strategies for managing iron dysregulation in chronic inflammatory diseases like CAP.

Impact of behavior change theory-based nursing interventions on cardiac function recovery and quality of life among cardiac surgery patients with cardiopulmonary bypass

BackgroundThis study investigates the impact of nursing interventions, guided by behavior change theory, on the recovery of cardiac function and quality of life in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).MethodsA total of 120 patients scheduled for CPB in the Department of Cardiology at our hospital, from February 2021 to May 2023, were enrolled. According to the study protocol, patients were randomly assigned to either a control group (n = 60) or an observation group (n = 60) post-surgery. The control group received routine nursing care, while the observation group received nursing interventions based on behavior change theory, including health education, psychological support, and behavioral incentives. Informed consent was obtained from all patients. General patient data were collected from clinical records. Cardiac function was assessed using echocardiography. The wall motion score index (WMSI) and 6-minute walk distance (6MWD) were evaluated post-care. Serum levels of inflammatory cytokines TNF-α, IL-6, and IL-10 were measured via ELISA. Quality of life was assessed using the WHOQOL-BREF questionnaire, while anxiety and depression levels were evaluated using the HAM-A and HAM-D scales, respectively.ResultsThe baseline clinical characteristics and biochemical data of both groups were comparable (P > 0.05). The observation group showed a significantly higher left ventricular ejection fraction (LVEF) compared to the control group (P < 0.05), while both left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were significantly lower (P < 0.05). Additionally, the observation group had a significantly lower WMSI score and a longer 6MWD (P < 0.05). Regarding inflammatory markers, TNF-α and IL-6 levels were significantly reduced in the observation group, while IL-10 levels were significantly elevated compared to the control group (P < 0.05). In terms of quality of life, the observation group reported significantly higher scores in physical health, mental health, social relationships, and environmental factors (P < 0.05). Moreover, anxiety and depression levels were significantly lower in the observation group, as evidenced by reduced HAM-A and HAM-D scores (P < 0.05).ConclusionNursing care guided by behavior change theory significantly improves cardiac function and overall quality of life in patients recovering from cardiac surgery with CPB. This approach enhances LVEF, reduces left intraventricular diameter, lowers inflammatory cytokine levels, and improves mental health and social functioning. These findings underscore the importance of behavior change theory-based nursing interventions in optimizing postoperative recovery.

Forsythiaside A Ameliorates Inflammation by Regulating the Autophagy in Methotrexate-induced Intestinal Mucositis.

Methotrexate (MTX) effectively eliminates cancerous cells but can also cause inflammation intestinal, known as mucositis. Forsythiaside A (FTA) from Forsythia suspensa has shown promise in relieving mucositis by targeting the NLRP3 pathways. Since NLRP3 inflammasome activation is negatively regulated by autophagy, this study explores how FTAmediated autophagy affects NLRP3 inflammasome in treating MTX-induced intestinal inflammation. Intestinal mucositis was induced in rats with MTX. FTA's impact was assessed using HE staining and ELISA. The mechanism was studied using immunofluorescence, western blot, and ELISA. FTA treatment resulted in reduced levels of D-lactic acid and diamine oxidase (DAO) in MTX-treated rats. Western blot and immunofluorescence analyses revealed up-regulation of Beclin- 1 and LC3II/I, accumulation of LC3, and down-regulation of p62 expression levels in MTXtreated rats following 40 or 80 mg/kg FTA intervention. However, when the autophagy inhibitor 3-MA was used, the intestinal pathology was exacerbated, the inflammatory scores increased, and serum levels of TNF-α, IL-1β, and IL-18 were elevated. Western blotting indicated decreased LC3II/I expression, while NLRP3, cleaved caspase 1, and cleaved IL-1β expressions were upregulated. These findings suggested that FTA alleviated MTX-treated intestinal mucositis by activating autophagy, which in turn inhibits the NLRP3 inflammasome.

Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage.

The immune heterogeneity of biliary atresia (BA) presents a challenge for development of prognostic biomarkers. This study aimed to identify early immune signatures associated with biliary drainage after Kasai Portoenterostomy (KPE). Serum samples, liver slides, and clinical data were obtained from patients enrolled in the NIDDK-supported Childhood Liver Disease Research Network. Serum cytokines and hepatic immune cell subsets were measured at diagnosis and compared among 3 groups: 38 infants with BA (20 with evidence of bile flow after KPE; 18 without) and 17 non-BA cholestatic infants. BA participants had lower numbers of lipid associated macrophages (LAM), and increased serum levels of Eotaxin-3, interleukin (IL) 12p70, and IL-8 versus non-BA groups (p < 0.05 for all). Among BA participants, monocyte like macrophages and serum levels of granulocyte-macrophage colony stimulating factor (GM-CSF) were increased in BA participants with good biliary drainage (p = 0.004 and p < 0.001 respectively). Levels of GM-CSF, IL-16, c-reactive protein, TNF-β predicted successful biliary drainage with an area under the receiver operating curve of 0.84 (p < 0.001). These findings suggest that distinct macrophage-associated immune networks at diagnosis may impact biliary drainage after KPE. Identification of early prognostic immune-modulatory markers has potential to improve patient stratification for medical and surgical therapies. We identify serum cytokines, particularly GM-CSF, that are associated with future biliary drainage in patients with biliary atresia. Characterization of macrophage-associated immune networks provides novel insight into early disease mechanism that may impact patient outcomes. Early prognostic biomarkers markers in biliary atresia can help in patient stratification for medical and surgical therapies.

Circulating Growth Factors and Cytokines Correlate with Temperament and Character Dimensions in Adolescents with Mood Disorders

Background/Objectives: The incidence of mood disorders in adolescents is increasing. Bipolar disorder is often misdiagnosed in the early stages of the disease due to the prevalence of depressive symptoms, while manic episodes occur later. Identifying predictors of diagnosis conversion could facilitate timely and appropriate treatment. Our study aimed to find correlations of selected peripheral protein levels with temperament and character traits in adolescents diagnosed with major depressive disorder and bipolar disorder. Methods: A group of adolescents and young adults diagnosed with major depressive disorder (MDD, n = 50) or bipolar disorder (BD, n = 24) was enrolled in the study during the exacerbation of symptoms and followed up over two years. Diagnosis conversion from MDD to BD was monitored. The Temperament and Character Inventory was applied, and BDNF, proBDNF, EGF, MIF, SCF, S100B, TNF-alpha, and IL-8 serum levels were measured. Spearman’s rank correlation analysis was conducted. Results: We found different patterns of correlations in MDD (TNF-alpha, IL-8, EGF, S100B with reward-dependence, self-directedness, and empathy) and BD (BDNF and EGF with persistence novelty-seeking and self-transcendence). Significant correlations were found in a group with diagnosis conversion. Conclusions: The findings of our study have the potential to significantly impact our understanding and treatment of mood disorders. Correlations obtained in the subgroup with diagnosis conversion may contribute to the development of prognostic markers in the future. Evaluating temperament and character traits alongside established biomarkers may offer a valuable method for predicting the conversion of mood disorders in adolescents, facilitating early and effective pharmacotherapy.

Pharmacological modulation of Sigma-1 receptor ameliorates pathological neuroinflammation in rats with diabetic neuropathic pain via the AKT/GSK-3β/NF-κB pathway.

Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP. However, it is not known whether Sig-1R can ameliorate pathological neuroinflammation in DNP. The present study used a rat model of DNP and a highly selective agonist of Sig-1R to assess the effects of the protein on neuropathic pain in rats with type 2 diabetes mellitus. The rats were divided into Control, Model, Sig-1R agonist PRE-084 (0.3, 0.6, 1mg/kg), and metformin (Met, 20mg/kg) groups, with seven rats per group, and their body weight, fasting blood glucose, mechanical withdrawal threshold and thermal withdrawal latency were tested weekly for two weeks. After treatment with PRE-084, the pain thresholds in the DNP rats were significantly improved, together with pathological changes in the dorsal root ganglion, reductions in the serum levels of TNF-α, IL-1β, IL-6, MOD, and prostaglandin E2 (PGE2), and the activity of superoxide dismutase was increased. The mRNA levels of TNF-α, IL-1β, and cyclooxygenase 2 (COX-2) were reduced. Pharmacological inhibition of Sig-1R with BD1047 (10μM) abolished Sig-1R-mediated activation of lipopolysaccharide-treated BV-2 microglial cells. It was also found that PRE-084 increased phosphorylation of serine/threonine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) at Ser9, inhibiting nuclear factor kappa B (NF-κB)-mediated neuroinflammation in the dorsal root ganglion, thus reducing DNP. The findings suggest that the effect of Sig-1R agonist PRE-084 on DNP may reduce the level of inflammation through the up-regulation of AKT/GSK-3β and down-regulation of the NF-κB signaling, thereby contributing to the treatment of the disease.

An animal model of severe acute respiratory distress syndrome for translational research

BackgroundDespite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.ResultsIn this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.ConclusionsThis modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Time-restricted feeding improves metabolic syndrome by activating thermogenesis in brown adipose tissue and reducing inflammatory markers

BackgroundObesity and metabolic syndrome (MetS) have become increasingly significant global health issues. Time-restricted feeding (TRF), as a novel dietary intervention, has garnered attention in recent years. However, there is limited research focusing on the effects of TRF on energy expenditure and systemic low-grade inflammation. This study aims to investigate the impact of TRF on weight management, glucose metabolism, insulin resistance, and lipid metabolism in male C57BL/6J mice, particularly in the context of metabolic disorders induced by a high-fat diet (HFD).MethodsC57BL/6J mice were divided into two groups: a normal diet (ND) group and a high-fat diet (HFD) group. The study duration was 12 weeks. Key parameters observed included body weight, glucose tolerance (via glucose tolerance tests), insulin resistance (HOMA-IR), and insulin secretion under glucose stimulation. Additionally, liver tissue was subjected to Oil Red O staining to assess lipid accumulation, and white and brown adipose tissues were stained with hematoxylin and eosin (HE) to evaluate adipocyte size. The expression of hepatic lipogenesis-related genes (Srebp-c, Chrebp, Fasn, and Acc1) and thermogenic genes in brown adipose tissue (UCP1 and PGC-1α) were also measured. Furthermore, temperature changes in the interscapular brown adipose tissue (BAT) were monitored.ResultsIn the ND group: TRF improved insulin resistance and reduced circulating levels of the pro-inflammatory cytokine IL-6, with a slight reduction in body weight.In the HFD group: TRF significantly mitigated weight gain, improved glucose tolerance and insulin resistance, and enhanced insulin secretion under glucose stimulation. Additionally, TRF reduced hepatic steatosis by downregulating the expression of lipogenesis-related genes in the liver. TRF also increased thermogenesis by upregulating the expression of thermogenic genes (UCP1 and PGC-1α) in BAT, while lowering serum levels of pro-inflammatory cytokines IL-6 and TNF-α, though IL-1β levels remained unchanged.ConclusionThis study demonstrates that TRF can activate thermogenesis in brown adipose tissue and reduce inflammation maker, leading to an improvement in hepatic steatosis and a reduction in white adipose tissue accumulation. These findings suggest that TRF may be a promising intervention for mitigating metabolic disturbances associated with obesity and metabolic syndrome. The study provides mechanistic insights into the beneficial effects of TRF, highlighting its potential in modulating lipid metabolism and exerting anti-inflammatory effects.

Assessment of Lactobacillus acidophilus (L. acidophilus) therapeutic and prophylactic role in rats experimentally infected with Blastocystis subtype 3 (ST3).

Blastocystis, an eukaryote, inhabits the intestinal tract of humans and animals worldwide. Lactobacillus acidophilus (L. acidophilus), a probiotic, has been reported to be effective against blastocystosis. The present study evaluated the therapeutic and prophylactic effectiveness of L. acidophilus compared to metronidazole (MTZ) in rats experimentally infected with Blastocystis subtype 3 (ST3). Four groups of Blastocystis ST3-infected rats received MTZ, L. acidophilus, both MTZ and L. acidophilus, or prophylactic L. acidophilus. Non-infected and infected control groups were included. The effectiveness of treatment and prevention was evaluated using parasitological monitoring, histopathological examination, immunohistochemical staining for TNF-α and IgA expression, and immunological testing for TNF-α and IL-10. In the L. acidophilus-treated group, a 76% reduction in the mean fecal parasitic count and a 67% clearance in the intestinal wash were achieved aligning closely with outcomes observed in the MTZ-treated group. An immunomodulatory impact via upregulation of the anti-inflammatory cytokine IL-10 and downregulation of the pro-inflammatory cytokine TNF-α was demonstrated as well. Combined administration of MTZ and L. acidophilus exhibited superior efficacy with a 99% decrease in the mean fecal parasitic count and a 98% decrease in the intestinal fluid parasitic count. Additionally, the lowest TNF-α and the highest IL-10 serum levels. Prophylactic use of L. acidophilus for 7 days neither prevented infection nor reduced its severity. Furthermore, no significant differences were detected in serum levels of TNF-α and IL-10 following post-prophylaxis andpost-treatmentwith L. acidophilus. Accordingly, L. acidophilus might be recommended as an adjuvant treatment alongside MTZ for improved efficacy against blastocystosis.

Association between serum levels of 12 different cytokines and short-term efficacy of chemoradiotherapy in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) has a poor prognosis, with chemoradiotherapy (CRT) being a key treatment method. This study focused on circulating cytokines as potential predictors of treatment response and prognosis in patients with ESCC.Materials and methodsSerum samples were collected from 36 ESCC patients, and 12 different cytokines were quantified using a multiplex immunofluorescence assay. We used non-parametric Wilcoxon unpaired rank tests to examine the relationship between cytokine concentrations and clinical outcomes. The duration of progression-free survival was assessed through imaging studies and telephone follow-ups. Kaplan–Meier survival plots, analyzed with the log-rank test, were utilized to depict survival trends.ResultsPre-treatment serum IL-8 levels were significantly elevated in patients with lymphoid metastases (p = 0.036). Lower initial levels of IL-8 and IL-1β were observed in patients with partial response group compared to those with stable disease (p = 0.002, p = 0.01). Elevated baseline levels of IL-8 and interferon-gamma (IFN-γ) were correlated with a poorer prognosis. Higher levels of IL-5 and IFN-γ levels following therapy were associated with worse outcomes.ConclusionsOur findings indicate that IL-8, IL-1β, IL-5, and IFN-γ may serve as potential biomarkers for treatment efficacy and prognosis in ESCC. Patients with low levels of IL-8 and IL-1β demonstrate a favorable response to CRT. Elevated serum levels of IL-8, IL-1β, IFN-γ, and IL-5 may predict poorer clinical outcomes.

Unclosing Clinical Criteria and the Role of Cytokines in the Pathogenesis of Persistent Post-COVID-19 Headaches: A Pilot Case-Control Study from Egypt

(1) Background: Persistent post-COVID-19 headaches are emerging as a significant post-infection symptom. This study investigates the clinical characteristics of persistent post-COVID-19 headaches and the potential role of pro-inflammatory cytokines. (2) Methods: We conducted a pilot case–control study involving 84 participants divided into three groups: post-COVID with headache (n = 28), post-COVID without headache (n = 28), and healthy controls (n = 28). The detailed headache characteristics, including pain intensity, were assessed using the Visual Analog Scale (VAS). The serum levels of inflammatory cytokines (IL-6 and TNF-α) were measured. (3) Results: Post-COVID headaches predominantly presented as bilateral (53.6%) and throbbing (60.7%) in nature, with a median of 12 headache days per month and high pain intensity (median VAS score = 80). The associated symptoms were phonophobia (85.7%), fatigue (78.6%), and photophobia (75%). The serum levels of IL-6 and TNF-α were significantly higher in post-COVID headache patients than in the post-COVID without headache and healthy control groups (p &lt; 0.001). A Receiver Operating Characteristic analysis showed that the circulating levels of IL-6 and TNF-α could discriminate our study groups at cutoffs with variable sensitivity and specificity. (4) Conclusions: Persistent post-COVID-19 headaches have diverse clinical characteristics and are associated with elevated circulating levels of pro-inflammatory cytokines, suggesting a potential underlying neuroinflammation.

P0431 Multiparametric Assessment of IBD, SpA and IBD-SpA patients to explore disease biomarkers and response predictors

Abstract Background Immune-mediated inflammatory diseases (IMID) can coexist within the same patient and their pathogenesis could overlap. Inflammatory bowel disease (IBD) [Crohn’s disease (CD) and ulcerative colitis (UC)], and spondylarthritis (SpA), often associate, but disease biomarkers are not fully characterized. This project aims to investigate a possible molecular signature of disease and predictor markers of response Methods We performed an observational prospective study, enrolling consecutive IMID patients (pts) starting a target therapy. We principally focused on 3 cohorts: IBD, SpA and IBD-SpA. At baseline, we performed a test for serum cytokines and also collected intestinal biopsies, to stain for immune cell markers. Clinical intestinal and articular response (CR) was assessed at 4, 12 and 24 months. CR was defined using clinical scores: Patient Reported Ouctome-2 (PRO-2) for UC and CD, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) for SpA Results We enrolled 134 pts (59 IBD, 75 SpA). All the SpA pts were seronegative with prevalent peripheric articular involvement. In the IBD cohort, 48% of the pts were naïve to advanced therapies, while the remaining part had been exposed to biologics. 34% pts were on concomitant steroid therapy at baseline. At baseline, we found lower serum levels of IL-6, IL-12/23, IL-7, IL-10, IL-33, IL-35 and IL-37 in IBD pts compared to SpA pts and that levels presented a direct or inverse correlation with the clinical scores (figure). In the IBD-SpA group, compared to the IBD group, we found higher levels of IL-6(p=0.001), sTREM1(p=0.027), IL10(p=0.002) and IL-37(p=0.016). According to PRO-2, 70% of pts were in steroid-free clinical remission at 12 months, and 81.8% at 24 months. Considering CR at 12 months, statistically significant differences were found in the groups of responders versus no responders. In the IBD cohort we found that 100% of responders, had low levels of IL-8(&amp;lt;8.6 pg/mL) and low CD117 cell count in intestinal tissue at baseline; besides, 80% of responders had high CD20 count in intestinal tissue at baseline. Kaplan-Meier curves for achieving CR at 24 months, in the entire cohort of pts, showed no statistically significant differences stratifying pts on demographic characteristics and type of disease Conclusion In IBD pts, we found results which could suggest a different systemic inflammation signature between IBD and SpA pts and the presence of possible biomarkers which, if confirmed, could help the physician in the early and non-invasive identification of the disease phenotype at diagnosis and response to therapies

CLINICAL CHARACTERISTICS AND SERUM CONCENTRATIONS OF SOME T-HELPER 2-DERIVED CYTOKINES IN PATIENTS WITH GENERALIZED ERYTHEMA MULTIFORME

Objective: To describe the clinical characteristics of patients with erythema multiforme (EM) presenting with generalized skin lesions and to investigate the serum concentrations of certain T-helper 2 (Th2) cytokines in these patients, exploring their correlation with specific clinical features. Subjects and Methods: This cross-sectional descriptive study included 33 patients diagnosed with EM featuring generalized skin lesions at the National Hospital of Dermatology and Venereology from April 2017 to August 2019. Additionally, 32 healthy controls (HCs) participated as the control group. Clinical examinations, medical history interviews, and serum sample collections were conducted for all subjects. The fluorescence covalent microbead immunosorbent assay technique was used to detect multiple cytokines simultaneously: IL-4, IL-5, and IL-13. The Mann-Whitney U test compared the serum cytokine levels between the two groups, with statistical significance set as p&lt;0.05. Pearson's test was applied to evaluate the correlation between two quantitative variables. Results: The mean age of EM patients with generalized lesions was 42.2 years; 30.3% were male, and 69.7% were female. Twenty-two patients (66.7%) had an illness duration of less than one week—a history of medication use before illness onset was reported by 60.6% of patients. Only 15.2% of patients had mucosal lesions. In the EM group, serum levels of IL-4 and IL-5 were 1.55±4.35 pg/ml and 7.12±18.91 pg/ml, respectively, which were lower than those in the HCs group (9.15±10.17 pg/ml and 21.38±20.85 pg/ml, respectively), p&lt;0.001. Serum IL-13 levels were identical in both groups (1.48 pg/ml). No correlation was found between serum IL-4 levels and age (r=0.08; p&gt;0.05), nor between serum IL-5 levels and age (r=-0.055; p&gt;0.05). Conclusion: Th2 cytokine levels in the EM group with generalized skin lesions were lower compared to the HCs group, with no correlation between these cytokine levels and age. Th2 is likely not an important factor in the pathogenesis of generalized EM. Received: 16 May 2023Revised: 24 June 2023Accepted: 22 July 2023

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays. We determined cytomegalovirus (CMV) serostatus and collected retrospective clinical information. We performed unsupervised and multivariable analyses. Unsupervised analyses revealed that MS immune profile was characterized by low relative levels of anti-inflammatory/neuroprotective factors IL-4, IL-10, TNF, and β-NGF but high levels of growth factors EGF and bFGF. Serum levels of IL-4, β-NGF, IL-27, BDNF, and leptin were significantly influenced by sex and/or CMV status. IL-4 and β-NGF levels were lower in untreated PwMS compared to controls, while EGF and bFGF levels were influenced by age and markedly elevated in PwMS in multivariable analysis. Samples from treated PwMS, but not untreated PwMS, showed lower levels of BDNF and TNF than controls. Initiation of high efficacy DMTs, but not low efficacy DMTs, was associated with reduced levels of bFGF and EGF. Samples associated with distinct DMTs exhibited specific profiles for age-sensitive immune markers. Finally, lower levels of IL-6, TNF, IL-10, and β-NGF were observed at baseline in PwMS who subsequently experienced clinical failure after DMTs initiation. Age, sex, CMV status, and specific DMTs significantly influence levels of age-sensitive immune biomarkers associated with MS and must be considered when investigating inflammation-related biomarkers. This work was supported by a Grant for Multiple Sclerosis Innovation by Merck KGaA (ID: 10.12039/100009945).

Characterization of serum and brain cytokine levels following prolonged binge-like methamphetamine self-administration and cued methamphetamine seeking.

Methamphetamine (METH) use is associated with peripheral and brain inflammation that can contribute to METH-associated toxicity and heightened cue reactivity. However, the persistence of these phenomena, especially with regards to changes in brain proinflammatory cytokine levels, is not yet clear. In this study, we determined the effects of repeated binge-like METH self-administration (96-h/week for 3weeks) followed by cued drug seeking for up to 60days into abstinence in male and female rats. Serum cytokine levels were assessed prior to cued drug seeking tests on days 21 and 60 of abstinence, and cytokine levels in the prefrontal cortex (PFC) and dorsal striatum (DStr) were assessed on the day following that last cued seeking test. We observed robust levels of METH intake in both sexes as well as a gradual increase in magnitude of METH seeking across abstinence that did not differ between sexes. Magnitude of METH seeking on days 10 and 60 were positively correlated with prior total drug intake. Sex- and region-dependent changes in various chemokines and interleukins were observed in the PFC and DStr, as were sex- and time-dependent changes in serum cytokine levels, with the largest number of cytokines altered on day 60 in male animals. Serum levels of IL-6 were positively correlated with brain levels of this cytokine, but serum levels of this and other cytokines did not correlate with the magnitude of METH seeking. These findings suggest that binge-like METH intake produces persistent yet divergent central and peripheral immune responses that extend well into abstinence.

Cross-Sectional Analysis of IL-6, TNF-α, Adiponectin, Leptin, and Klotho Serum Levels in Relation to BMI Among Overweight and Obese Children Aged 10-14 in La Rioja, Spain.

Childhood obesity is a major public health concern, being linked to an increased risk of metabolic disorders and cardiovascular disease. Even in childhood, obesity is associated with systemic low-grade inflammation, which is a critical factor in the development of atherosclerosis and a predictor of cardiovascular morbidity and mortality. To describe the prevalence of obesity and examine the relationship between IL-6, TNF-α, adiponectin, leptin, the leptin/adiponectin (L/A) ratio, and Klotho levels with BMI in children. This cross-sectional study included children aged 10-14 years from La Rioja, Spain. Participants were selected based on BMI criteria for overweight (85th-95th percentiles) and obesity (>95th percentile). Socio-demographic and anthropometric data and blood samples were collected and analyzed for IL-6, TNF-α, adiponectin, leptin, and Klotho. A total of 340 participants were included, with 276 (81.2%) classified as normal weight and 64 (18.8%) as overweight or obese. Mean age was similar between groups (p = 0.40). Obesity was more prevalent in males (59.4%, p = 0.048). Obese participants had higher mean birth weight (p = 0.003), current height (p = 0.04), BMI (p < 0.0001), and abdominal circumference (p < 0.0001). BMI correlated positively with leptin (r = 0.54, p = 0.0008) and the L/A ratio (r = 0.40, p = 0.025), showing sex-specific differences. This study underscores leptin and the L/A ratio as potential biomarkers of metabolic dysregulation in childhood obesity, particularly in females. Longitudinal studies are needed to confirm these findings and assess the clinical utility of these biomarkers in pediatric obesity management.

Assessment of inflammatory markers in Acne vulgaris patients: serum IL-17, IL22, and IL-10

One of the four main factors in the pathophysiology of acne vulgaris (AV) is inflammation, which may be a primary or secondary process caused by Propionibacterium acnes. To counteract inflammatory mediators, the immune system possesses a variety of anti-inflammatory mechanisms. The data supporting the early involvement of the inflammatory pathway in the etiology of AV, a chronic, complex, inflammatory skin condition, has become more clear. This cell line's activators, Th17 cells, and the cytokines that follow are all probably important in initiating and maintaining the disease. The aim of this study is to determine the degree to which acne vulgaris is influenced by the interleukins IL-10, IL-17, and IL-22. Individualized patients in our study, sex-matched controls were included, and there were 42 male and 58 female AV patients, aged 12 to 30. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of IL-10, IL-17, and IL-22. The levels were then connected with the severity of acne. In cases, the serum levels of IL-10, IL-17, and IL-22 were 0.34±0.080, 0.13, 0.14±0.0035, 0.136-0.233, and 0.24±0.0142, 0.126-0.243 pg/ml, respectively, while in controls, they were 0.13±0.028, 0.10±0.0085, 0.14±0.0035, 0.117-0.126, and 0.22±0.0089, 0.114-0.127 pg/ml. For IL-10 and IL-17, there was a substantial difference in levels between patients and controls; however, for IL-22, the difference was negligible. The levels of IL-10 and IL-17 showed an extremely strong positive connection. This study came to the conclusion that IL-10 and IL-17 are important effectors in the pathophysiology of AV. In acne lesions, Th17 cells activated by IL-22 are probably the main source of IL-37.

Frailty and osteoporotic fractures represent mutual risks for each other with common physiological backgrounds

Abstract Frailty and osteoporosis are known to exacerbate each other. However, limited research is available on the shared pathophysiological factors contributing to osteoporotic fractures and frailty. This study aims to identify common factors associated with both the current frailty and the occurrence of incident vertebral fractures. A total of 912 postmenopausal Japanese women, 63.9 ± 10.0 years of age (mean ± SD), were included in the present study. Each participant’s baseline frailty status was assessed using a questionnaire about the five following items: Fatigue, Resistance, Ambulation, Inactivity, and Weight Loss. A score of 3 or above indicated the prevalence of frailty. The participants were then followed up for an average of 10.5 ± 7.5 years, during which 202 patients suffered incident vertebral fractures. The Cox proportional hazards model for incident vertebral fracture revealed that lumbar bone mineral density (HR 0.753, P&amp;lt;.001), adiponectin (HR 1.025, P=.021), Log IL-6 (HR 1.227, P=.029), prevalent vertebral fracture (HR 2.124, P&amp;lt;.001), and frailty status (HR 1.355, P=.002) were independent predictors of incident vertebral fractures. The factors associated with frailty status at baseline were assessed using logistic regression analysis, revealing that adiponectin (OR 1.063, P&amp;lt;.001), Log IL-6 (OR 2.94, P&amp;lt;.001), and prevalent vertebral fractures (OR 2.816, P&amp;lt;.001) were significantly associated with current frailty. Biochemical factors such as IL-6 and adiponectin were commonly associated with vertebral fractures and frailty. Additionally, frailty status was identified as an independent risk factor for vertebral fractures, while prevalent vertebral fractures were significantly associated with frailty. These findings clearly indicate that frailty and osteoporotic fractures represent mutual risks for each other, with serum levels of adiponectin and IL-6 serving as common physiological backgrounds.

Serum interleukin-6 and associated nociceptive parameters following subcutaneous infiltration of lidocaine alone, tramadol alone, and their combination in red Sokoto goat undergoing rumenotomy

The clinical practice of combining one or more drugs is gaining attention for enhancing efficacy, leading to quicker onset of action, longer duration of effect and minimising side effects. Previous studies showed that combining lignocaine and tramadol in an epidural injection significantly extended the duration of analgesia produced when compared to the use of lignocaine alone. The significance of this study is aiming toward improved pain management during surgery, especially in goats. In this study, the analgesic effects of subcutaneously administered lignocaine alone (7 mgkg-1), tramadol alone (3 mgkg-1), and their respective combination of 3.5 and 15 mgkg-1 on pain in goats undergoing rumenotomy were compared. The experiment was carried out on fifteen healthy (N=15) Red Sokoto goats. Blood was drawn from the jugular vein at seven distinct time intervals during the course of the experiment (0, 1, 2, 3, 4, 5, 6 and 7 hours) and serum was extracted. The severity of pain was ascertained by measuring serum level of IL-6 and the nociceptive response to a pain stimulus using a clinical algometer. This study revealed that the combination of lidocaine (03.78 minutes) and tramadol (3.68 minutes) has a quicker onset of action (2.01±0.42 minutes) and a more extended duration of activity (79.5 minutes) when compared to lidocaine (60 minutes) and tramadol (55.75 minutes) administered separately. There was no significant difference (P&gt;0.05) in serum IL-6 before and after the administration of lidocaine, tramadol, or their combination. This study has demonstrated that the lidocaine-tramadol combination at respective doses of 3.5 and 1.5 mgkg-1 has a quicker onset and longer duration of activity when subcutaneously administered at the surgical site, in comparison with lidocaine alone and tramadol alone at respective doses of 7 and 3 mgkg-1. However, there was no remarkable difference in the serum pain biomarker (IL-6) among the three different treatments. Subcutaneous infiltration of the combination of lidocaine at 3.5 mgkg-1 with tramadol at 1.5 mgkg-1 via the inverted L block technique can be employed as an alternative to conventional lidocaine alone to achieve loco-regional analgesia for a more prolonged duration in goats to conduct laparotomy. Clinically, this drug combination could be useful in surgeries requiring extended regional anaesthesia, reducing the need for repeated dosing, hence improving animal welfare.