Elevated Interleukin-6 Levels Research Articles

Prediction of Clinical Severity of COVID-19 Using a Combination of Heparin-Binding Protein, Interleukin-6, and C-Reactive Protein: A Retrospective Study.

Systemic inflammation stands as a pivotal factor tightly interwoven with the progression of COVID-19. This study endeavors to elucidate the significance of three key inflammatory molecules, that is, heparin-binding protein (HBP), interleukin-6 (IL-6), and C-reactive protein (CRP), in assessing the severity and prognostic implications of COVID-19. The demographic, clinical, and laboratory data were retrospectively collected from a cohort of 214 adult patients diagnosed with COVID-19. Patients were divided into two groups: nonsevere (n = 93; 43.5%) and severe (n = 121; 56.5%). Additionally, based on their organ function, patients were categorized into nonorgan failure (n = 137) and organ failure (n = 77) groups. The levels of inflammation-related cytokines were then compared among these defined groups. The severe group was characterized by a higher proportion of males, older age, and longer hospital stays compared to nonsevere cases. Additionally, severe cases exhibited a higher prevalence of underlying diseases and organ failure. Statistical analysis revealed significantly elevated levels of HBP, IL-6, and CRP in the severe group. HBP, IL-6, and CRP were identified as independent risk factors for severe COVID-19. Furthermore, a combined assessment of these biomarkers demonstrated superior diagnostic sensitivity (85.10%) and specificity (95.70%) for predicting COVID-19 severity. A positive relationship between elevated HBP, IL-6, and CRP levels and impaired organ function was also observed. The predictive efficiency significantly increased (hazard ratio = 3.631, log-rank p = 0.003) when two or more of them were combinedly used. Notably, elevated levels of HBP, IL-6, and CRP were associated with an increased risk of mortality. In conclusion, the combined assessment of HBP, IL-6, and CRP offers enhanced accuracy and specificity in predicting the severity, organ failure, and mortality risk associated with COVID-19.

Investigating Interleukin-6 Levels in Type 2 Diabetes Mellitus Patients With and Without Diabetic Nephropathy.

Diabetic nephropathy (DN), a severe complication affecting 40% of diabetic individuals, is a leading cause of chronic kidney disease (CKD). It involves a progressive increase in urinary albumin and a decline in the glomerular filtration rate. Early detection and intervention are crucial to preventing CKD progression. The current marker, albuminuria, measured as the urine albumin-to-creatinine ratio (UACR), has limitations, highlighting the need for alternative biomarkers. Researchers have linked the proinflammatory cytokine interleukin-6 (IL-6) to the progression of DN, observing elevated levels in DN patients compared to those without DN. IL-6 also regulates glucose metabolism, promoting insulin effectiveness and secretion. Inflammation and glucose control are two things that IL-6 does. This makes it a promising biomarker and therapeutic target for DN and type 2 diabetes mellitus (T2DM). This study focuses on IL-6 levels in T2DM patients with and without DN. From September 2022 to June 2024, the Department of General Medicine, Dr. D. Y. Patil Medical College, Hospitaland Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University),Pune, conducted an observational cross-sectional comparative study on 80 T2DM patients, with 40 in group A (cases = T2DM patients with DN) and 40 in group B (controls = T2DM patients without DN). The study included patients with T2DM between the ages of 40 and 80. The study excludes conditions such as diabetic ketoacidosis, patients with end-stage renal disease, and conditions that increase IL-6, such as COVID-19. The study excluded autoimmune conditions with elevated IL-6, such as rheumatoid arthritis, systemic lupus erythematous, ankylosing spondylitis, psoriasis, and Crohn's disease. We obtained ethical approval and written consent from participants. In the current study, 61 patients (76.2%) were 60 years old or younger, while 19 patients (23.8%) were older than 60 years. Among the participants, 38 were females (47.5%) and 42 were males (52.5%). The case group, which consisted of 40 T2DM patients with DN, had a mean glycated hemoglobin (HbA1c) of 7.1700 ± 0.71044. In contrast, the control group, comprising 40 T2DM patients without DN, had a mean HbA1c of 6.8650 ± 0.57179. This difference was statistically significant, with a p value of 0.038. Additionally, the mean UACR in the case group was 134.34 ± 95.56, significantly higher than the control group's mean UACR of 22.32 ± 9.90. This difference was highly significant, with a p value of 0.001. Furthermore, the case group exhibited elevated mean IL-6 levels of 15.48 ± 4.27 compared to the control group's 7.02 ± 2.46, which is also highly significant, reflected by a p value of 0.001. As the concentration of IL-6 rises in diabetic patients with nephropathy, this study suggests that IL-6 may have an effect on the development of DN. This cytokine is necessary for both the initiation and progression of the condition. Using IL-6 as a supportive diagnostic test could help rule out other potential causes of DN in T2DM. Moreover, this marker does not require invasive procedures, and early measurement may help reduce mortality and morbidity.

Pre-treatment with tocilizumab reduces lipopolysaccharide-induced acute lung injury in biliary cirrhotic rats

Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-α (TNF-α). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-α and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-α, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-α and CD68-positive macrophage recruitment in the lung.

Cutaneous Plasmacytosis Treated with Tocilizumab.

Cutaneous plasmacytosis is a rare disorder of unknown etiology characterized by the proliferation of mature plasma cells in the skin and polyclonal hypergammaglobulinemia. Cutaneous plasmacytosis is associated with an elevated Interleukin-6 level. Anti-IL-6 therapy has not been reported as a therapy for idiopathic cutaneous plasmacytosis. This article presents a case of a Caucasian woman with idiopathic cutaneous plasmacytosis who was successfully treated with tocilizumab, a monoclonal anti-IL-6 receptor antibody. The patient experienced improvement in both her cutaneous lesions as well as subjective symptoms after 2 months on tocilizumab.

Interleukin-8 in HepG2 cells: Enhancing antiviral proteins in uninfected cells but promoting HBV replication in infected cells

In vitro studies have revealed that hepatitis B virus (HBV) infection upregulates interleukin-8 (IL-8), which enhances HBV replication. Clinically, elevated IL-8 levels in chronic HBV patients are associated with diminished therapeutic efficacy of interferon-α (IFN-α). Our study advances these findings by demonstrating that IL-8 promotes the expression of myxovirus resistance A (MxA) and protein kinase R (PKR) in HepG2 cells via the PI3K-AKT pathway. However, HBV-infected cells fail to exhibit IL-8-induced upregulation of MxA and PKR, likely due to HBV's upregulation of PP2A that inhibits the PI3K-AKT pathway. Notably, IL-8 targets the C/EBPα transcription factor, increasing HBV promoter activity and viral replication, which in turn partially suppresses the expression of MxA and PKR induced by IFN-α. Our findings uncover a mechanism by which HBV may evade immune responses, suggesting potential new strategies for immunotherapy against chronic HBV infection.

Differential inflammatory profiles in carriers of reciprocal 22q11.2 copy number variants

BackgroundGenetic copy number variants (CNVs; i.e., a deletion or duplication) at the 22q11.2 locus confer increased risk of neuropsychiatric disorders and immune dysfunction. Inflammatory profiles of 22q11.2 CNV carriers can shed light on gene-immune relationships that may be related to neuropsychiatric symptoms. However, little is known about inflammation and its relationship to clinical phenotypes in 22q11.2 CNV carriers. Here, we investigate differences in peripheral inflammatory markers in 22q11.2 CNV carriers and explore their relationship with psychosis risk symptoms and sleep disturbance. MethodsBlood samples and clinical assessments were collected from 22q11.2 deletion (22qDel) carriers (n=45), 22q11.2 duplication (22qDup) carriers (n=29), and typically developing (TD) control participants (n=92). Blood plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and anti-inflammatory cytokine interleukin-10 (IL-10) were measured using a MesoScale Discovery multiplex immunoassay. Plasma levels of C-reactive protein (CRP) were measured using Enzyme-linked Immunosorbent Assay (ELISA). Linear mixed effects models controlling for age, sex, and body mass index were used to: a) examine group differences in inflammatory markers between 22qDel, 22qDup, and TD controls, b) test differences in inflammatory markers between 22qDel carriers with psychosis risk symptoms (22qDelPS+) and those without (22qDelPS-), and c) conduct an exploratory analysis testing the effect of sleep disturbance on inflammation in 22qDel and 22qDup carriers. A false discovery rate correction was used to correct for multiple comparisons. Results22qDup carriers exhibited significantly elevated levels of IL-8 relative to TD controls (q<0.001) and marginally elevated IL-8 levels relative to 22qDel carriers (q=0.08). There were no other significant differences in inflammatory markers between the three groups (q>0.13). 22qDelPS+ exhibited increased levels of IL-8 relative to both 22qDelPS- (q=0.02) and TD controls (p=0.002). There were no relationships between sleep and inflammatory markers that survived FDR correction (q>0.14). ConclusionOur results suggest that CNVs at the 22q11.2 locus may have differential effects on inflammatory processes related to IL-8, a key mediator of inflammation produced by macrophages and microglia. Further, these IL-8-mediated inflammatory processes may be related to psychosis risk symptoms in 22qDel carriers. Additional research is required to understand the mechanisms contributing to these differential levels of IL-8 between 22q11.2 CNV carriers and IL-8’s association with psychosis risk.

The dichloromethane fraction from Calotropis gigantea (L.) dryand. Stem bark extract prevents liver cancer in SDT rats with insulin-independent diabetes mellitus

Ethnopharmacological relevanceCalotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments. AimThis study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy. Materials and methodsSpontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression. ResultsRats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-β1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage. ConclusionsThese findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.

Assessment of Cardiometabolic Risk Factors and Insulin Sensitivity by Hyperinsulinemic-Euglycemic Clamp in Resistance to Thyroid Hormone β Syndrome.

Background: Resistance to thyroid hormone beta (RTHβ) is a rare disease resulting from mutations in the THRB gene, characterized by reduced T3 action in tissues with high thyroid hormone receptor β expression. Thyroid hormones regulate body composition and metabolism in general, and increased or decreased hormone levels are associated with insulin resistance. This study evaluated the presence of cardiometabolic risk factors and insulin sensitivity in patients with RTHβ. Methods: In all, 16 patients, 8 adults (52.3 ± 16.3 years of age) and 8 children (10.9 ± 3.9 years of age), were compared to 28 control individuals matched for age, sex, and body mass index (BMI). Anthropometry evaluation and blood samples were collected for glycemia, lipids, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, ultrasensitive C-reactive protein (CRPus), free thyroxine, total triiodothyronine, thyrotropin, and anti-thyroid peroxidase measurements. Body composition was assessed using dual-emission X-ray absorptiometry and bioimpedance. Insulin sensitivity was evaluated in adult patients and controls using the hyperinsulinemic-euglycemic clamp (HEC), whereas homeostasis model assessment of insulin resistance (HOMA-IR) was calculated in all individuals studied. Results: Patients and controls presented similar weight, BMI, abdominal perimeter, and total fat body mass. Patients with RTHβ demonstrated higher total cholesterol (TC), p = 0.04, and low-density lipoprotein cholesterol (LDL-C), p = 0.03, but no alteration was observed in other parameters associated with metabolic risk, such as leptin, TNF-α, and CRPus. Two adult patients met the criteria for metabolic syndrome. There was no evidence of insulin resistance assessed by HEC or HOMA-IR. Elevated IL-6 levels were observed in patients with RTHβ. Conclusion: Using HEC as the gold standard method, no evidence of reduced insulin sensitivity in skeletal muscle was documented in RTHβ adult patients; however, higher levels of TC and LDL-C were observed in these patients, which suggest the need for active monitoring of this abnormality to minimize cardiometabolic risk. In addition, we demonstrated, for the first time, that the increase in IL-6 levels in patients with RTHβ is probably secondary to metabolic causes as they have normal levels of TNF-α and CRPus, which may contribute to an increase in cardiovascular risk. A larger number of patients must be studied to confirm these results.

Enviromental endocrine disruptor risks in the central nervous system: Neurotoxic effects of PFOS and glyphosate

Endocrine disruptors (EDs) pose significant risks to human and environmental health, with potential implications for neurotoxicity. This study investigates the synergistic neurotoxic effects of perfluorooctane sulfonate (PFOS) and glyphosate (GLY), two ubiquitous EDs, using SHSY5Y neuronal and C6 astrocytic cell lines. While individual exposures to PFOS and glyphosate at non-toxic concentrations did not induce significant changes, their combination resulted in a marked increase in oxidative stress and neuroinflammatory responses. Specifically, the co-exposure led to elevated levels of interleukin-6, tumor necrosis factor alpha, and interferon gamma, along with reduced interleukin-10 expression, indicative of heightened neuroinflammatory processes. These findings underscore the importance of considering the synergistic interactions of EDs in assessing neurotoxic risks and highlight the urgent need for further research to mitigate the adverse effects of these compounds on neurological health.

Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population

BackgroundAtherosclerosis is an inflammatory disease. Interleukin 18 (IL-18) is an inflammatory molecule that has been linked to the development of atherosclerosis and cardiovascular disease. ObjectiveTo evaluate the possible relationship between plasma levels of IL-18 and the presence of atherosclerosis evaluated at the carotid level, as well as to analyze the possible modulation by different polymorphisms in a Mediterranean population. Material and methods746 individuals from the metropolitan area of ​​Valencia were included, recruited over a period of 2 years. Hydrocarbon and lipid metabolism parameters were determined using standard methodology and IL-18 using ELISA. In addition, carotid ultrasound was performed and the genotype of 4 SNPs related to the IL-18 signaling pathway was analyzed. ResultsPatients with higher plasma levels of IL-18 had other associated cardiovascular risk factors. Elevated IL-18 levels were significantly associated with higher carotid IMT and the presence of atheromatous plaques. The genotype with the A allele of the SNP rs2287037 was associated with a higher prevalence of carotid atheromatous plaque. On the contrary, the genotype with the C allele of the SNP rs2293224 was associated with a lower prevalence of atheromatous plaque. ConclusionsHigh levels of IL-18 were significantly associated with a higher carotid IMT and the presence of atheromatous plaques, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the IL-18 receptor gene and the presence of atheroma plaque.

Systematic Review on the Role of IL-6 and IL-1β in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a leading cause of global morbidity and mortality, significantly driven by chronic inflammation. Interleukin-6 (IL-6) and interleukin-1β (IL-1β) are critical inflammatory cytokines implicated in CVD progression. This systematic review evaluates the roles of IL-6 and IL-1β in CVDs by synthesizing data from relevant studies to understand their impact on cardiovascular outcomes and identify potential therapeutic interventions. A comprehensive literature search was conducted using PubMed and Embase, covering studies from January 2014 to December 2024. Inclusion criteria encompassed studies investigating IL-6 and/or IL-1β in CVDs, including human and relevant animal models, and reporting clinical outcomes, molecular mechanisms, or therapeutic interventions. Data extraction and quality assessment were performed independently by two reviewers. Our review included 12 studies focusing on the roles of IL-6 and IL-1β in various CVDs. Elevated IL-6 levels were significantly associated with peripheral artery disease, myocardial infarction, and heart failure, while IL-1β levels were linked to worse outcomes in coronary artery disease and heart failure. Meta-analyses indicated a significant association between higher IL-6 and IL-1β levels and increased risk of adverse cardiovascular events. These findings suggest that targeting IL-6 and IL-1β could offer promising therapeutic strategies for reducing inflammation and improving cardiovascular outcomes.

Impact of sleep deprivation on stress levels and cognitive performance in young and middle-aged adults at a Medical University in Ajman, UAE.

Inadequate sleep is a widespread public health concern, impacting physical and mental health, as well as cognitive well-being. This study explores the link between sleep quality, the inflammatory marker interleukin-6 (IL-6), and cognitive function in two age groups (18-25 years and 35 years and above) at Gulf Medical University. Sleep quality was assessed using the Pittsburgh questionnaire, and salivary IL-6 levels were measured. Cognitive function was evaluated using the National Aeronautics and Space Administration-Psychomotor Vigilance Test (NASA-PVT), focusing on mean reaction time (RT), lapses, fastest 10% RT, and slowest 10% RT. Descriptive and inferential statistics were used to analyze the data. The descriptive statistics used were frequency, percentage mean, and standard deviation (SD). The inferential statistics used was the unpaired t-test. The level of significance was taken as P ≤ 0.05. Statistical Package for the Social Sciences (SPSS) 28 was used to analyze the data. Approximately 75% of young adults and 80% of middle-aged adults reported good sleep quality. Sleep disturbances were reported by 65% of young adults and 95% of middle-aged adults. In both age groups, individuals with poor sleep exhibited higher IL-6 levels, but all IL-6 values remained within the reference range. NASA-PVT results indicated that individuals with poor sleep had higher mean RT and lapses compared to those with good sleep. In the older age group, both mean RT and lapses were higher than in the younger group, suggesting potential age-related effects on psychomotor vigilance. Our findings suggest a connection between poor sleep quality, elevated IL-6 levels, and impaired cognitive performance.

Interleukin-8 is a potential inflammation biomarker in major depressive disorder

BackgroundThe neuroinflammatory hypothesis of Major Depressive Disorder (MDD) postulates that dysregulated cytokine production is implicated in the etiopathology of the disorder. This study aimed to determine baseline levels of Interleukin-8 (IL-8), an inflammatory cytokine, in MDD and identify possible changes in response to antidepressant drug therapy. MethodsTwo independent groups of MDD patients who met study criteria were enrolled; one group was treated with Escitalopram and the other with Quetiapine for twelve weeks. There was a healthy control (HC) group. In the Escitalopram group 30 patients completed the baseline visit and in the Quetiapine group 43 patients. Plasma concentrations of IL-8 were measured at baseline, week eight, and week 12 of treatment. IL-8 levels were correlated with depression severity at baseline and week 12. The sample size for IL-8 analysis was 17 study completers in the Escitalopram study, 21 study completers in the Quetiapine study, and 19 HCs. We used the Student's t-test and the Pearson Correlation Coefficient for statistical analyses. ResultsMDD patients exhibited elevated IL-8 levels at baseline compared to healthy controls (p = 0.007). However, IL-8 levels did not show a significant reduction after 12 weeks of treatment and were not significantly correlated with depression severity at either baseline or week 12 of treatment. However, there was a notable downtrend in IL-8 levels after treatment in both groups though not statistically significant. LimitationsStudy limitations include sample size variations and power, and study length. No formal assessment was conducted to rule out Axis II diagnoses. ConclusionsThese findings underscore the relationship between IL-8 and MDD, suggesting that IL-8 may play a role in the pathophysiology of MDD, but its relationship with antidepressant treatment requires a prolonged period of treatment. This study suggests a role for IL-8 in MDD as a pro-inflammatory biomarker, while the lack of immediate normalization post-treatment indicates the need for further exploration of delayed effects of antidepressant therapy on immune markers and IL-8′s relationship with the mechanism of action of specific pharmacotherapies used in MDD.

Pilot study: Significance of I-FABP2 in the diagnosis of acute abdominal episodes in children

BackgroundPediatric abdominal conditions, including necrotizing gastrointestinal diseases, pose significant diagnostic challenges due to clinic symptoms and limited diagnostic tools. Intestinal fatty acid binding protein 2 (I-FABP2) has emerged as a potential biomarker for intestinal damage, but its efficacy in diagnosing pediatric intestinal necrosis remains under explored. MethodsA prospective study was conducted on 55 pediatric patients presenting with abdominal pain and suspected intestinal necrosis or intestinal perforation. Clinical, laboratory, and radiological data were collected, and intraoperative assessment of bowel necrosis was performed. Gene expression of I-FABP2 in peripheral blood was measured using Real-Time RT-PCR, and correlations with surgery and laboratory parameters were analyzed. ResultsIntraoperative assessment revealed a moderate sensitivity (61.1%) and specificity (73.7%) of I-FABP2 in identifying bowel necrosis. Positive predictive value (PPV) was high (81.5%), indicating a high likelihood of the condition when I-FABP2 is positive. However, the negative predictive value (NPV) was limited (50%), suggesting challenges in confidently excluding necrosis based on negative I-FABP2 results. Correlations were observed between I-FABP2 expression and elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC), indicating its association with inflammatory processes. ConclusionsWhile I-FABP2 shows promise as a biomarker for pediatric intestinal necrosis, its diagnostic utility may be enhanced when considered alongside other clinical parameters. Further research and validation studies are warranted to refine its clinical application and improve diagnostic accuracy in pediatric gastrointestinal conditions.

SARS-CoV-2 Induced Interleukin -18 Response among Presumptive Covid-19 Patients in Kano State, Nigeria

Study’s Novelty/Excerpt This study evaluates Interleukin-18 (IL-18) as a potential biomarker for COVID-19 by comparing its serum levels in COVID-19-positive patients and healthy controls. The research uniquely identifies significantly elevated IL-18 levels in COVID-19 patients, demonstrating a strong statistical association with the infection (t value 6.16, p &lt;0.00010). These findings underscore the potential of IL-18 in the prognosis and clinical management of COVID-19, offering new insights into its role in the disease's pathophysiology and its utility as a biomarker. Full Abstract Coronaviruses have a history of causing severe outbreaks with life-threatening consequences, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the recent coronavirus disease 2019 (COVID-19). COVID-19 first broke out in Wuhan (China) in December 2019). The disease was later declared a pandemic, and so far, more than 222 countries have been affected, with over 771 million confirmed cases and total deaths of over 7.05 million. Some immunological markers were reported elsewhere as directly related to COVID-19 pathophysiology and stand a chance to be considered biomarkers. Interleukin 18 (IL-18) is a proinflammatory cytokine and a member of the interleukin-1 family, produced by macrophages at the early stage of viral infections. However, aberrant IL-18 production can lead to severe pathological injury. Hence, there is a need to assess the feasibility of interleukin -18 as a biomarker for COVID-19. Forty-five individuals diagnosed with COVID-19 and 45 healthy controls screened using a COVID-19 antigen rapid test kit and confirmed by one-step real-time PCR were recruited for this study. Blood samples were collected from the patients and controls, and the samples were analyzed for IL-18 using the ELISA technique. This study revealed a higher level of IL-18 in COVID-19-positive patients (206.42 ± 13.2 pg/mL) compared to the control group (97.96 ± 14.4 pg/mL). Serum level IL-18 was statistically associated with COVID-19 infection (t value 6.16, p &lt;0.00010). The study demonstrates the importance of IL-18 in the COVID-19 cohort, inferentially implying its potential in the prognosis and clinical management of COVID-19.

Anti-inflammatory Effect of Apigenin Obtained by Portulaca oleracea L in ‎Male Mice

This study aimed to evaluate the potential anti-inflammatory effects of ‎‎apigenin, obtained from Portulaca oleracea L., using a male mouse model‎. A total of 56 ‎healthy BLAB/c albino male mice (Mus musculus) were used in two experiments. In the first experiment‎, ‎the xylene-induced ear edema, 28 male mice were randomly divided into four groups (n=7). ‎The negative control group received distilled water, while the positive control, apigenin-‎treated, and indomethacin-treated groups were exposed to xylene (0.03 mL applied to ‎the anterior and posterior surface of the right ear lobe) to induce inflammation. ‎Subsequently, the apigenin-treated group received orally 50 mg/kg BW apigenin, and ‎the indomethacin-treated group received orally 0.36 mg/kg BW indomethacin.‎ Ear weight ‎difference was calculated as an indicator ‎of anti-inflammatory. For the second experiment, the carrageenan-induced paw edema‎, a ‎similar experimental design was followed, but carrageenan (50 ‎mg/kg BW of 1% solution) ‎was ‎administered intra-dermally‎ in the right hindpaws.‎ Paw skin thickness difference ‎and differential white blood ‎cells (WBCs) count, along with the ‎quantification of prostaglandin E-2 ‎‎(PGE-2) and ‎interleukin-6 (IL-6) in serum samples, were used as indicators of anti-inflammatory.‎ Results showed that xylene exposure led ‎to a significant ear weight increase, ‎indicative of ‎inflammation. Conversely, the ‎apigenin-treated group demonstrated a ‎reduction in ear ‎weight compared to the positive control group. Similarly, carrageenan ‎administration resulted ‎in a substantial ‎increase in paw skin thickness and elevated levels of ‎WBCs count, PGE-2, ‎and IL-6. ‎Apigenin treatment significantly mitigated these ‎inflammatory markers, ‎‎outperforming indomethacin in PGE-2 ‎and IL-6‎. This study provides evidence supporting the potential ‎of P. oleracea-derived ‎apigenin as an effective anti-inflammatory agent, showing ‎comparable or better ‎efficacy ‎than indomethacin‎‎‎‎‎.

Blood clot properties, thrombin generation, and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

There is a strong link between coronary artery disease (CAD), type 2 diabetes (T2D) on one hand, and altered fibrin clot properties, including increased clot density, and unfavorable fibrin clot structure on the other. T2D-related changes in fibrin clots can increase cardiovascular (CV) disease risk, including future CV events. We aimed to assess fibrin clot properties, thrombin generation, and platelet activation in CAD patients with prediabetes (PD) or T2D, compared to CAD patients without glycemic disorders. We allocated patients to three groups: 1) Those with angiographically established CAD but without glycemic abnormalities (CAD group); 2) individuals with PD and established CAD (CAD+PD group); and 3) patients with T2D and CAD (CAD+T2D group). We conducted comparisons across these groups for thrombin generation, fibrin clot permeability, fibrin clot lysis, and platelet activation. The final analysis included 116 eligible patients: 1) CAD group (n = 31); 2) CAD+PD (n = 42); and 3) CAD+T2D (n = 43). The CAD+T2D patients enrolled had well-controlled T2D (median HbA1c level of 5.90%; IQR: 5.7%-6.3%). We found no significant differences in thrombin generation, fibrin clot properties, or platelet activation markers across the three analyzed groups (all P-values >0.20). However, elevated interleukin-6 (IL-6) levels were noted in both the highest and lowest glucose concentration quartiles. Additionally, a substantial increase in endogenous thrombin potential (ETP) was observed in patients in the highest glycated hemoglobin quintile. Individuals with established CAD and concomitant PD or well-controlled T2D exhibited comparable fibrin clot phenotypes, thrombin generation potential, and platelet activation when compared to CAD patients without dysglycemia.

Assessment of interleukin-18 gene polymorphism and serum levels in cutaneous lichen planus

BackgroundLichen planus (LP) is a chronic inflammatory disease with uncertain etiology. Interleukin-18 (IL-18) is an interferon gamma (INFγ) inducing agent. It is a pro-inflammatory cytokine that was found to play a role in the pathogenesis of some autoimmune disorders.Material and methodsThis study included 50 patients with classic cutaneous lichen planus (CLP) and 50 healthy volunteers serving as controls. Venous blood samples were withdrawn from the study subjects under complete aseptic precautions. Blood samples were examined for single nucleotide polymorphisms (SNPs) of IL-18 gene at promoter -137(G/C) and -656 (G/T) using polymerase chain reaction (PCR) and IL-18 level was assessed using enzyme linked immunosorbent assay (ELISA).ResultsThe mean level of IL-18 was significantly higher in CLP patients (31.63 ± 4.90) compared to control subjects (13.95 ± 6.82). Significantly high levels of IL-18 were found among patients with diabetes, hypertension (p < 0.01 in both). HCV positive patients and patients with both OLP and CLP also expressed higher levels of IL-18. Genotypic and allelic distribution at position -137(G/C) showed that the genotype GG was present at significantly higher frequency in cases (58%) compared to controls (28.0%). On the other hand the CC genotype at position -137 was significantly higher in the controls (28%) as compared to CLP cases (6%). Polymorphism of IL-18 at position -656(G/T) showed no significant difference between cases and controls. No significant difference could be detected in IL-18 level between different genotypic variants at position -137(G/C) and -656(G/T).ConclusionIL-18 may play important role in pathogenesis of LP. Elevated IL-18 levels could be part of the pro-inflammatory autoimmune process in LP. The presence of OLP, HCV, diabetes and hypertension is associated with higher production of IL-18. IL-18 promotor region -137(G/C) polymorphism might be a factor that increase the risk of development of lichen planus in Egyptian patients.

Serum IL-6 as a Surrogate Biomarker of Post-operative Complications in Invasive Orthopaedic Surgeries: A Prospective Observational Study.

Interleukin-6 (IL-6) is a cytokine released in response to tissue injury. Elevated serum IL-6 levels in trauma patients have been linked with increased risk of complications such as inapparent hypoxia (SpO2 < 94%), acute respiratory distress syndrome, fat embolism syndrome (FES), systemic inflammatory response syndrome, multiple organ dysfunction syndrome and sepsis. This study aims to determine the role of serum IL-6 as surrogate biomarker of post-operative complications after invasive orthopaedic surgeries. Thirty-seven adults between 18 and 65years of age undergoing invasive orthopaedic surgeries were included in this hospital-based study. Serum IL-6 levels were estimated serially in the pre-operative period, after 24h and 7days post-operatively. Cases were monitored for post-operative complications. Serum IL-6 levels showed maximum rise in the first 24h post-operatively especially among older patients (> 60years). Older patients undergoing bipolar hemiarthroplasty for neck of femur fracture showed highest median post-operative IL-6 level of 258pg/ml. Serum IL-6 level > 130pg/ml measured 24h after surgery was predictive of post-operative complications (sensitivity of 75%). Among the cases with post-operative complications, inapparent hypoxia was the most common complication/event observed. Cases with sub-clinical FES had highest level of serum IL-6 in first 24h following surgery with median IL-6 level of 300pg/ml (range 155-444 pg/ml). Monitoring serum IL-6 level may help in both anticipation and early detection of post-operative complications in patients undergoing invasive orthopaedic surgeries; potentially enhancing patient safety.

The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions.

Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.