Interleukin-17 Levels Research Articles

The Combined Administration of Eicosapentaenoic Acid (EPA) and Gamma-Linolenic Acid (GLA) in Experimentally Induced Colitis: An Experimental Study in Rats

Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited effective treatments, prompting the need for investigation of novel therapeutic approaches. Eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) have demonstrated potential anti-inflammatory properties, but their combined effects on UC have not been thoroughly investigated. This study aimed to evaluate the effect of the combined administration of EPA and GLA on clinical and histopathologic features of experimental UC models. Methods: Thirty-six male Wistar rats were randomized in three groups (DSS group, Ensure Plus group, and Oxepa group), with twelve rats in each group. Experimental colitis was induced by administrating dextran sulfate sodium (DSS) 8%. The DSS group received tap water, the Ensure Plus group was given a high caloric diet, and the Oxepa group received a special diet containing high levels of EPA and GLA. Disease activity index (DAI) and microscopic activity index (MAI) were measured. Inflammatory markers were calculated both in blood and large intestine, liver, spleen, and lung tissue samples. Neutrophil and macrophage populations were assessed with immunohistochemistry. Results: No significant differences in the DAI index were found between the groups, but the MAI revealed statistically significant differences (p < 0.001). While no significant differences were observed in tumor necrosis factor-alpha (TNF-α) levels, interleukin-17 (IL-17) levels in the large intestine showed statistically significant differences (p = 0.05), with the Ensure Plus and Oxepa groups displaying lower levels compared to the DSS group (p = 0.021 and p = 0.043, respectively). Significant differences in neutrophil infiltration were found in both the large intestine (p < 0.001) and lungs (p = 0.002), with the Oxepa group showing fewer cells. Similarly, significant differences in macrophage infiltration were observed in the large intestine (p = 0.038) and spleen (p < 0.001), with the Oxepa group having lower macrophage counts. Conclusions: In conclusion, the combination of EPA and GLA demonstrates local anti-inflammatory effects and improves the histopathological outcomes in UC.

Interleukin 37 Role in Diabetic Iraqi Patients: A comparison between patients treated with and without Insulin

Background: Diabetes Mellitus (DM) is defined as a metabolic disorder that is characterized by some clinical features, such as chronic hyperglycemia accompanied by impairment of carbohydrates metabolism, proteins, and lipids. However, relative or absolute insulin deficiency is associated with the high blood glucose levels, which is attributed to the β-cells dysfunction, insulin resistance or could be both. The anti-inflammatory cytokine interleukin-37 (IL-37) negatively regulates inflammation, therefore, reduces inflammation and alters metabolic pathways. It acts by suppressing inflammatory cytokines and chemokines, activation of IL-37 inhibits inflammation and obstructs the infiltration of pro-inflammatory cells, primarily neutrophils and eosinophils. Aim of Study: The estimation of IL 37 and other biochemical parameters in patients with Diabetes mellitus and study its role in the pathogenicity of the disease. Materials and methods: A case-control study design was adopted to study the relationship between Interleukin 37 and insulin treatment in Nasiriyah in the Diabetes and Endocrinology Specialized Center between December 2023 and January 2024. It was conducted on patients with Diabetes Mellitus type 2 (60 patients) divided into two groups (30 patients treated with Insulin injection) and (30 patient treated with oral tab only). On the other hand, 30 people were taken as a control group without Diabetes Mellitus.Result: Patients with diabetes mellitus have been noticed to have higher levels of IL-37 in comparison to the healthy control groups. In general, patients with diabetes mellitus have higher levels of IL-37 compared to three groups, G1, G2, and healthy control groups. Conclusion We demonstrated that serum levels concentration of IL 1b and IL 37 significantly increased in our patients also FBS, HbA1c, Insulin Resistance, HOMO IR, TG, cholesterol, and decrease C- peptide as compared to healthy individuals.

Potential pro-tumour cytokine in oral squamous cellular carcinoma: IL37.

Inflammation and immunosuppression are important features of tumours, including oral squamous cellular carcinoma (OSCC). Interleukin 37 (IL37), a cytokine known for the ability to suppress inflammation and immunity, shows two seemingly contradictory functions in tumours. This study aims to investigate the mechanism that regulates IL37 and its role in OSCC progression. Herein, IL37, CD86 and CD206 in OSCC specimens were determined. Hypoxia, MCC950 and siRNA-Gasdermin D (GSDMD) were utilised to investigate the mechanism of IL37 production and release. Animal experiments were established to examine the role of IL37 in OSCC growth invivo. We found the levels of IL37 are elevated in OSCC tissues compared with normal oral mucosa. In cell experiments, hypoxia was proved to be a vital facilitator in IL37 expression and release. Mechanically, hypoxia promoted IL37 expression through the activation of NACHT-LRR-PYD-containing protein 3 (NLRP3) inflammasome, and promoted IL37 release via GSDMD. Furthermore, IL37 levels in OSCC specimens are positively correlated with the number of M2 macrophages, but negatively with M1. Further studies revealed IL37 facilitated OSCC progression via promoting macrophage polarization from M1 to M2 and enhancing tumour cell proliferation. Thus, IL37 could be a promising target for OSCC treatment in the future.

Effect of Vitamin D Supplementation on Inflammatory Markers in Obese Patients with Acute and Chronic Orthopedic Conditions

Numerous studies have shown that vitamin D may play an important role in modulating the inflammatory process. This study aimed to evaluate the effect of vitamin D supplementation on inflammatory markers in patients with orthopedic disorders and obesity. Thirty-three obese subjects were included in the study and were divided into two groups based on their medical condition: acute orthopedic diseases and chronic orthopedic diseases. Inclusion criteria for the research included age 18–75 years, BMI > 30 kg/m2, vitamin D deficiency, and no previous vitamin D supplementation. Samples were collected before and after 3 months of 4000 IU/day vitamin D supplementation. The study used enzyme-linked immunosorbent assay (ELISA) and measured serum levels of markers such as chitinase-3-like protein 1 (YKL-40), interleukin 6 (IL-6), interleukin 17 (IL-17), tumor necrosis factor (TNF-α), and adiponectin. After 3 months of vitamin D supplementation, a statistically significant increase in vitamin D and IL-17 levels was observed in the group with acute orthopedic diseases. Similarly, after supplementation, a statistically significant increase in vitamin D, IL-6 and TNF-α levels was observed in the group with chronic orthopedic diseases. Moreover, after vitamin D supplementation, statistically significantly higher adiponectin levels were observed in the chronic orthopedic group than in the acute orthopedic group. Despite high-dose vitamin D supplementation, inflammatory markers increased in acute and chronic orthopedic conditions. Based on our study, vitamin D does not reduce inflammation in patients with orthopedic conditions and obesity.

Changes of vitamin D, Th17/Treg related cytokines and their correlations with disease activity in chronic spontaneous urticaria

AimsTo investigate levels of 25-hydroxyvitamin-D (25HVD), interleukin-17 (IL-17), IL-27, IL-35, and transforming growth factor β1 (TGF-β1) in chronic spontaneous urticaria (CSU) patients and their correlations with disease activity.MethodsAn observational, case-control study was conducted. Eighty-one CSU patients and fifty-eight healthy individuals were recruited into two groups. Serum levels of 25HVD, IL-17, IL-27, IL-35, TGF-β1 were determined via enzyme-linked immunosorbent assay (ELISA). Disease activity of CSU was assessed using urticaria activity score (UAS).ResultsSerum level of 25HVD was significantly lower in CSU group compared to control group (P < 0.001). Serum levels of IL-17 (P < 0.001), IL-27 (P < 0.001), TGF-β1 (P = 0.01) were significantly higher in CSU group than those in control group. In CSU group, the level of 25HVD was negatively associated with IgE (P < 0.01) and positively correlated with IL-35 (P < 0.01). In addition, serum level of IL-17 was negatively correlated with disease activity among female patients (P < 0.05).ConclusionDeficiency of 25HVD is associated with development of CSU, the underlying mechanism might be related with IL-35. Likewise, IL-17, IL-27, IL-35, and TGF-β1 might also contribute to development of CSU.

Alpha-Pinene-encapsulated lipid nanoparticles diminished inflammatory responses in THP-1 cells and imiquimod-induced psoriasis-like skin injury and splenomegaly in mice

IntroductionPsoriasis, a persistent skin condition caused by the disorder of the immune system, impacts approximately 1.25 million individuals globally. Nevertheless, the presence of adverse effects in conventional clinical drugs necessitates further exploration of novel medications or combination therapies to mitigate these reactions and enhance their effectiveness.MethodsHence, our intention here in this paper is to utilize the lipid nanoparticle delivery system for overcoming the volatility and hydrophobic properties of α-pinene, a naturally occurring compound renowned for its anti-inflammatory and antiviral effects, and further explore its potential pharmacological applications both in vitro and in vivo.ResultsThe production of α-pinene lipid nanoparticles (APLNs) was achieved through the utilization of high pressure homogenization methods. APLNs was successfully fabricated with enhanced stability and water solubility. Meanwhile, the application of APLNs could drastically reduce the expression of lipopolysaccharide (LPS)-induced inflammation-related factors in THP-1 cells. Administration of APLNs to a mouse model of auricular swelling could effectively reduce redness and swelling in the auricles of mice as well. Furthermore, APLNs were also found to alleviate skin damage in mice with Imiquimod (IMQ)-induced psoriasis model, as well as decrease the levels of psoriasis-related protein nuclear factor kappa-B (NF-κB) and interleukin-17 (IL-17), interleukin-23 (IL-23), and other inflammation-related cytokines. More importantly, utilization of APLNs successfully mitigated the systemic inflammatory reactions in mice, resulting in the reduction of spleen-to-body ratio (wt%) and of inflammatory cytokines’ expression in the serum.DiscussionOverall, our results suggest that with the help of lipid nanoparticle encapsulation, APLNs possess a better pharmacological effect in anti-inflammation and could potentially serve as an anti-psoriasis drug.

Interleukin 21, plasminogen activator inhibitor 1 and fractalkine improve risk stratification in elderly patients with pulmonary embolism

Abstract Background The importance of clinical parameters for predicting short-term mortality in hemodynamically stable patients with pulmonary embolism (PE) is acknowledged within the Pulmonary Embolism Severity Index (PESI) Score. Little is known about the value of novel biomarkers in this context. Given the pathophysiology of PE, markers related to inflammation and thrombosis, such as interleukin 21 (IL-21), fractalkine and plasminogen activator inhibitor 1 (PAI1) are of particular interest. Purpose To identify new protein biomarkers that improve 90d mortality prediction compared to the PESI score in elderly PE patients. Methods 1003 patients with venous thromboembolism aged ≥65 years were recruited between 2009 and 2011 from 9 hospitals in Switzerland (SWITCO65+ cohort). Among these, 778 patients were excluded due to missing data, deep venous thrombosis only, blood sample taken >1 day after diagnosis, no initial anticoagulation, systolic blood pressure <90 mmHg, withdrawal within 1 day or denying further use of data; 225 patients were prospectively included. Outcome was independently adjudicated up to 1 year after the index event. To identify candidate proteins, untargeted proteomic analyses (OLINK) were conducted in cases with 90d all-cause mortality (n=20) matched 1:2 (age, sex) to controls without events (n=40). 26 candidate proteins were then validated in all 225 PE patients using ELISA and Mesoscale analyses. Using ROC analyses, the most promising proteins to predict death within 90d were identified within this cohort. Optimal biomarker cut-off levels were derived using the Youden Index and survival analyses were computed. To evaluate the predictive value of these biomarkers, hazard ratios (HR) were calculated after adjusting for age, sex, and BMI. AUC-ROC analyses were performed to assess the biomarkers’ value for risk prediction compared to the PESI score. Results Baseline characteristics (Figure 1) did not differ between patients who died within 90d and those who did not, except for median PESI score (108 [95 – 125] vs. 87 [79 – 101], p<0.001). Optimal biomarker cut-off values were: IL-21: 56.17pg/ml, PAI1: 36.82pg/ml, fractalkine: 66’515pg/ml. Increased levels of IL-21 and PAI1 were associated with increased mortality (HR IL-21 = 1.5 [95% CI: 0.99 - 2.79], HR PAI1 = 2.6 [95% CI: 1.7 – 4.8]), whereas patients with elevated fractalkine levels were at lower risk to die within 90d (HR fractalkine = 0.37 [95% CI: 0.16 - 0.60]). For prediction of 90d mortality, the three assessed biomarkers showed a higher AUC than the PESI score. Combining the PESI score with the biomarkers did not further improve the AUC (Figure 2). Conclusions The protein biomarkers IL-21, PAI1 and fractalkine improve prediction of 90d mortality in elderly, hemodynamically stable PE patients compared to the PESI score. These biomarkers highlight the contribution of inflammation and thrombosis in the pathophysiology of PE and warrant further investigation.Baseline CharacteristicsROC Curves for Biomarkers and PESI Score

IL-27 attenuated macrophage injury and inflammation induced by Mycobacterium tuberculosis by activating autophagy.

Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection.Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting.Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1β, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response.Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB.

Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study.

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study's objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum IL17 and TLR4 levels. A total of 43 patients with MASLD (MASH/MAFL) and 38 healthy individuals were genotyped for IL17F-A7488G, IL17A-G197A, TLR4-Asp299Gly, and TLR4-Thr399Ile polymorphisms using PCR-RFLP. ELISA methods determined IL17F, IL17A, and TLR4 serum levels. (3) Conclusions: Patients carrying the variant genotypes (A/G + G/G) of IL17-A7448G (OR = 5.25), (G/A + A/A) of IL17-G197A (OR = 10.57), (Asp/Gly + Gly/Gly) of TLR4-Asp299Gly (OR = 3.52), or (Thr/Ile + Ile/Ile) of TLR4-Thr399Ile (OR = 9.87) had significantly increased odds of MASH. Genotype (G/A + A/A) of IL17-G197A was significantly associated with the odds of MAFL (p = 0.0166). Allele A of the IL17-G197A polymorphism was significantly related to increased odds of MAFL (OR = 4.13, p = 0.0133). In contrast, allele A of IL17-G197A (OR = 5.41, p = 0.008), allele Gly of TLR4-Asp299Gly (OR = 3.19, p = 0.046), and allele Ile of TLR4-Thr399Ile (OR = 6.94, p = 0.008) polymorphisms were significantly related to an increased risk of MASH. Allele A of IL17A-G197A, allele Gly of TLR4-Asp299Gly, and allele Ile of TLR4-Thr399Ile gene polymorphisms were significantly associated with the increased odds of MASLD. In patients with MASLD, we found significant influence from the IL17A-G197A gene polymorphism on IL17F levels (p = 0.0343).

Eutopic and Ectopic Endometrial Interleukin-17 and Interleukin-17 Receptor Expression at the Endometrial-Myometrial Interface in Women with Adenomyosis: Possible Pathophysiology Implications.

Adenomyosis involves the infiltration of endometrial glands and stroma deep into the uterine tissue, causing disruption to the endometrial-myometrial interface (EMI). The role of interleukin-17 (IL-17) has been extensively studied in endometriosis, but its involvement in adenomyosis remains unclear. This study aimed to investigate the expression of IL-17 in eutopic and ectopic endometrium (adenomyosis) of individuals with adenomyosis at the level of EMI. Paired tissues of eutopic endometrium and adenomyoma were collected from 16 premenopausal women undergoing hysterectomy due to adenomyosis. The IL-17 system was demonstrated in paired tissue samples at the level of EMI by the immunochemistry study. Gene expression levels of IL-17A and IL-17 receptor (IL-17R) were assessed through quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Comparative gene transcript amounts were calculated using the delta-delta Ct method. By immunohistochemical staining, CD4, IL-17A, and IL-17R proteins were detected in both eutopic endometrium and adenomyosis at the level of EMI. IL-17A and IL-17R were expressed mainly in the glandular cells, and the expression of both IL-17A and IL-17R was found to be stronger in adenomyosis than in endometrium. 3-Diaminobenzidine (DAB) staining revealed greater IL-17A expression in adenomyosis compared to eutopic endometrium. Quantitative RT-PCR showed 7.28-fold change of IL-17A and 1.99-fold change of IL-17R, and the fold change level of both IL-17A and IL-17R is significantly higher in adenomyosis (IL-17A: p = 0.047, IL-17R: p = 0.027) versus eutopic endometrium. We found significantly higher IL-17 levels in adenomyosis compared to eutopic endometrium at the level of EMI. The results showed that the IL-17 system may play a role in adenomyosis.

Effect of oral doxycycline, azithromycin and isotretinoin on haematological inflammatory markers and interleukin-17A levels in acne vulgaris: a single blinded randomised interventional study.

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32 ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216 ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17A levels. Baseline levels of IL-17A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated.

Expression of neutrophil extracellular trap-related proteins and its correlation with IL-17 and TNF-α in patients with oral lichen planus.

Neutrophil extracellular traps (NETs) are produced by polymorphonuclear neutrophils (PMNs) stimulated by interleukin-17 (IL-17) and tumor necrosis factor α (TNF-α). However, the level and role of NETs in oral lichen planus (OLP) remain poorly understood. This study aimed to investigate the expression of NETs in OLP and explore the correlation between NETs and the levels of IL-17 and TNF-α. The expression and distribution of NET-related proteins in tissue samples from each group were assessed using hematoxylin-eosin (HE) staining and immunofluorescence (IF). Additionally, the expression of NET-related proteins in peripheral blood samples from each group was evaluated using cell IF technique and fluorescence spectrophotometry. The relative formation level of NETs in each group was determined by fluorescence spectrophotometry via plasma co-culture. Furthermore, the levels of inflammatory cytokines IL-17 and TNF-α in plasma and culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA). NET-related proteins were located in the subepithelial and lamina propria layers of OLP lesions. OLP had significantly higher expression of NET-related proteins in lesion tissues and peripheral blood compared to the healthy control (HC) group (p < 0.05). The rate of NETs formation in the erosive-stage OLP (EOLP) group was significantly higher than that in the HC group (p < 0.05), in contrast, no significant increase was observed in the non-erosive OLP (NEOLP) group (p > 0.05). Furthermore, the levels of IL-17 and TNF-α in the EOLP group were significantly elevated compared to those in the NEOLP group and HC group (p < 0.05), while the levels in the NEOLP group did not significantly differ from those in the HC group (p > 0.05). The rate of NETs formation showed a positive correlation with the levels of IL-17 and TNF-α in plasma. The expression of NET-related proteins was upregulated in OLP lesion tissues and peripheral blood. Elevated levels of IL-17 and TNF-α in peripheral blood plasma positively correlated with the rate of NETs formation, suggesting that IL-17 and TNF-α mediate the formation of NETs in OLP patients, and may thereby contribute to the development of OLP.

Association of Celiac Disease and H. pylori Infection with ATG5 Polymorphism and Interleukin-33

Background: Celiac disease (CD) is an inflammatory small intestine autoimmune disease. The study aims to investigate the association and the detection of ATG5 polymorphism between celiac disease (CD) and H. pylori infection, and the association with Interleukin-33 (IL-33).Methods: The study groups included patients from Iraq, ages 4 to 35. Two primary patient groups were created: sixteen had positive H. pylori and celiac disease, and thirty had positive CD and negative H. pylori disease. The levels of tissue transglutaminase IgA (TTG IgA), H. pylori IgG, and IL-33 were measured using the ELISA method. The primers were amplified using PCR.Results: With celiac disease, the patient group's TTG IgA levels increased dramatically. The test also showed significant variations (P=0.054) in the H. pylori IgG levels between the patient and control groups. The H. pylori seropositivity test showed a statistically significant difference (p ≤0.033) between seropositive and seronegative individuals, while the patient group's IL-33 levels did not significantly differ (P ≤0.299) from the control group.Conclusions: Our results showed that CD is more common in women and occurs in the age range of 24-35 years. It also showed that the mutant variant of ATG5 is associated with CD, and the significance of H. pylori IgG serum levels in the patient group may indicate that the bacteria involved in CD. Furthermore, H. pylori infection is more strongly linked to serum IL-33 levels than CD.Keywords: Celiac disease; H. pylori; PCR; IL-33; ATG5 polymorphism

Interleukin-22 improves ovulation in polycystic ovary syndrome via STAT3 signaling.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. A disturbance of the ovarian immune microenvironment contributes to the disorders of follicle development and ovulation; however, the underlying mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with oocyte fertilization rate and high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells. This indicates that IL-22 acts through IL-22R1 and the STAT3 signaling pathway to promote follicle development and ovulation in PCOS. In summary, this study has elucidated the vital role of the ovarian immune microenvironment in follicle development and ovulation. Application of IL-22 may provide new insights into the treatment of PCOS patients.

Elevated serum IL-17 A and CCL20 levels as potential biomarkers in major psychotic disorders: a case-control study

BackgroundMajor psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics.MethodWe conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS).ResultsThe mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1–15.3) pg/mL and 4.2 (3–5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20.ConclusionThe current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia.

Emerging Roles of IL-27 in Trophoblast Cells and Pregnancy Complications.

Pregnancy complications such as spontaneous abortion, preeclampsia, and preterm birth persist, despite current interventions aimed at their prevention and treatment largely proving unsuccessful. Interleukin-27 (IL-27), composed of p28 and EBI3 subunits, binds to IL-27R, which consists of gp130 and IL-27Rα (also known as WSX-1 or TCCR), and plays a pivotal role in tumor development and inflammation regulation. At the maternal-fetal interface, IL-27 expression has been detected in trophoblasts, endometrial stromal cells, and decidual cells. Abnormal levels of IL-27/IL-27R have been linked to adverse pregnancy outcomes, including spontaneous miscarriage, preeclampsia, and preterm birth. This review aims to explore the expression of IL-27 at the maternal-fetal interface and its signaling pathway, uncovering the complex role of IL-27 in pregnancy complications. A comprehensive literature review was conducted using PubMed/Medline, Scopus, and Embase databases, analyzing studies on IL-27 expression and its signaling pathways at the maternal-fetal interface. The review focused on identifying the presence of IL-27 in various cell types and linking abnormal IL-27/IL-27R expression to pregnancy complications such as spontaneous miscarriage, preeclampsia, and preterm birth. IL-27 plays a complex role at the maternal-fetal interface, with abnormal expression linked to several pregnancy complications. These findings highlight the need for further research to elucidate IL-27's mechanisms and develop targeted interventions. Future studies should aim to develop targeted interventions and improve therapeutic strategies for managing pregnancy complications.

The Effect of Metformin Therapy on Serum IL-33 and ST-2 Receptor Levels in Patients With Type 2 Diabetes Mellitus

Introduction: Patients with type 2 had elevated levels of inflammatory biomarkers, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF-α). Significant elevations in serum levels of TNF-α and C-reactive protein were seen in individuals with type 2 diabetes mellitus (T2DM). The IL-1 superfamily (IL-1β, IL-18, and IL-33) plays a crucial role in the development of diabetes mellitus by modifying immunological and inflammatory immune responses. Objectives: Little is known about the role of metformin in type 2 diabetes mellitus with respect to serum levels of IL-33 and ST-2 receptors. Therefore, in the present study, we sought toexplore such role. Patients and Methods: This single arm study included 45 type 2 diabetes patients with an age range of 30 to less than 60 years. Patients were given metformin (500 mg orally; for two months then, serum level of interleukin- 33 (IL-33) and ST-2 receptors were evaluated. Results: Treatment resulted in significant reduction of serum the suppression of tumorigenicity suppressor 2 (ST2) from 0.71 ±0.157 µg/mlto 0.59 ±0.11 µg/ml (p&lt;0.001), across with significant increase in serum IL-33 from 0.60 ±0.18 pg/ml to 0.75 ±0.13 pg/ml (p &lt; 0.001). Conclusion: Treatment of type 2 diabetes mellitus using metformin revealed a crucial role for IL-33 and ST-2 receptors in glycemic control since increment in IL-33 and reduction in ST-2 receptors were associated with good glycemic control suggesting an inflammatory role in disease pathogenesis and response to treatment.

Association of serum interleukin-17 level and Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis.

Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen of community-acquired pneumonia. Interleukin-17 (IL-17) plays a role in host defense and contributes to disease severity in infection. This present study aims to investigate the association between Mycoplasma pneumoniae pneumonia (MPP) and changes of IL-17 level in the serum of pediatric patients. The protocol has been registered in PROSPERO (CRD42023489451). A literature search was conducted in PubMed, EMBASE, Scopus, and Web of Science from inception to October 2023. A meta-analysis was performed to pool the mean difference (MD) with 95% confidence intervals (CIs) of IL-17 levels between patients and controls. Publication bias was assessed, and the risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). Out of 207 records, 10 studies were included in the review and 9 studies were included in the meta-analysis. Of these, 7 studies compared IL-17 in general MPP patients with controls, 6 studies compared severe MPP patients with mild MPP patients. Serum IL-17 levels were significantly elevated in general MPP patients compared with control (MD =33.94 pg/mL, 95% CI: 24.66, 43.22 pg/mL, P=0.01, I2=99.07%; P=0.01). Subgroup analyses showed a difference in serum IL-17 levels treated by macrolide between patients and control (MD =83.96 pg/mL, 95% CI: 76.62, 91.29 pg/mL, P=0.01). In severe and mild MPP, the IL-17 levels were significantly increased (MD =19.08 pg/mL, 95% CI: 11.51, 26.65 pg/mL, P=0.01) and heterogeneity was appeared (I2=99.39%; P=0.01). For the risks of bias, two studies had a "high risk" in comparability domain, and the 7 studies were classified as "low risk" and "unclear risk". Our meta-analysis revealed that serum IL-17 levels are significantly elevated in pediatric with general and severe MPP. IL-17 might be a potential biomarker or therapeutic target for pneumonia caused by M. pneumoniae.

No association between serum prolactin and IL-17 levels in patients with hyperprolactinemia, rheumatoid arthritis, and systemic lupus erythematosus

Prolactin is a female hormone contributing to the production of milk in women with the immunologic functions. Moreover, it contributes to the pathogenesis of some diseases such as autoimmune diseases, and hyperprolactinemia. Previous studies showed interleukin 17 (IL-17) contributes to the pathogenesis of autoimmune diseases. Given the prolactin may exert its pathologic effects through increasing IL-17 level, the levels of prolactin, and IL-17 were quantified, and their association was evaluated in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and hyperprolactinemia patients. Therefore, the association between prolactin, and IL-17 levels in hyperprolactinemia, RA, and SLE patients was evaluated in this study. Four groups, including healthy individuals (n = 50), RA (n = 50), hyperprolactinemia (n = 50) and SLE (n = 35) were entered into the study. Patients were diagnosed according to the internationals criteria for recognition of RA, hyperprolactinemia and SLE. To measure the serum levels of prolactin, and IL-17, the ELISA method was used. Correlation analysis of prolactin, and IL-17 levels in each group showed that no association exists between the levels of the prolactin, and IL-17 in each group (p value &gt; 0.05). Unexpectedly, patients in two autoimmune groups, RA and SLE, did not demonstrate significantly elevated level of prolactin (P-value &gt; 0.05). In another unexpected finding, IL-17 level was not significantly higher in SLE patients (P-value &gt; 0.05). Altogether, our results suggest that there was no association between prolactin, and IL-17 levels in hyperprolactinemia, RA, and SLE.

Assessment of serum levels of ischemia modified albumin and interleukin-17 in children with atopic dermatitis.

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in childhood. Interleukin 17 (IL17) is one of the pro-inflammatory cytokines that has an important role in the pathogenesis of many skin diseases including AD. Ischemia modified albumin (IMA) is an indicator of oxidative stress, inflammation and ischemia. The aim of the study was to assess the IL-17 and IMA serum levels in the children patients with AD in comparison to a control group. Additionally, the study seeks to examine the correlation between these biomarkers and their association with disease severity, disease stages, and other clinical characteristics. The case-control study enrolled two groups: (patient group: 50 children with AD) and (control group: 50 healthy age and sex-matched children). Full history was taken from all cases along with full dermatologic examination. The assessment of AD severity was conducted by using Eczema Area and Severity Index (EASI). Evaluation of IL-17 and IMA was performed by using ELISA technique. There was a statistically significant elevation in the mean levels of IL-17 and IMA in patients with AD compared to the control group. A strong positive correlation was observed between IL-17 and IMA levels. Additionally, both IL-17 and IMA levels exhibited a statistically significant negative correlation with the duration of the disease and the age of the patients. The elevated serum levels of IL17 and IMA and their positive correlation confirm that AD is a systemic inflammatory disease influenced and associated with increased oxidative stress.