Serum IL-18 Levels Research Articles

Mechanistic role of RND3-regulated IL33/ST2 signaling on cardiomyocyte senescence

Hyperinflammatory responses are pivotal in the cardiomyocyte senescence pathophysiology, with IL33 serving as a crucial pro-inflammatory mediator. Our previous findings highlighted RND3's suppressive effect on IL33 expression. This study aims to explore the role of RND3 in IL33/ST2 signaling activation and in cardiomyocyte senescence. Intramyocardial injection of exogenous IL33 reduces the ejection fraction and fractional shortening of rats, inducing the appearance of senescence-associated secretory phenotype (SASP) in myocardial tissues. Recombinant IL33 treatment of AC16 cardiomyocytes significantly upregulated expression of SASP factors like IL1α, IL6, and MCP1, and increased the p-p65/p65 ratio and proportions of SA-β-gal and γH2AX-positive cells. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) and ST2 antibody astegolimab treatments mitigated above effects. RND3 gene knockout H9C2 cardiomyocytes using CRISPR/Cas9 technology upregulated IL33, ST2L, IL1α, IL6, and MCP1 levels, decreased sST2 levels, and increased SA-β-gal and γH2AX-positive cells. A highly possibility of binding between RND3 and IL33 proteins was showed by molecular docking and co-immunoprecipitation, and loss of RND3 attenuated ubiquitination mediated degradation of IL33; what's more, a panel of ubiquitination regulatory genes closely related to RND3 were screened using qPCR array. In contrast, RND3 overexpression in rats by injection of AAV9-CMV-RND3 particles inhibited IL33, ST2L, IL1α, IL6, and MCP1 expression in cardiac tissues, decreased serum IL33 levels, and increased sST2 levels. These results suggest that RND3 expression in cardiomyocytes modulates cell senescence by inhibiting the IL33/ST2/NF-κB signaling pathway, underscoring its potential as a therapeutic target in cardiovascular senescence.

Assessment of serum inflammatory parameters in RRMS and SPMS patients

ABSTRACT Objectives Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Patients with relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) differ in their responses to treatment; therefore, the correct diagnosis of the particular type of MS is crucial, and biomarkers that can differentiate between the forms of MS need to be identified. The aim of this study was to compare the levels of inflammatory parameters in serum samples from patients with RRMS and SPMS. Methods The study group consisted of 60 patients with diagnosed MS. The patients were divided into RRMS and SPMS groups. In the RRMS patients, the usage of disease-modifying treatment was included in our analysis. The serum levels of inflammatory parameters were evaluated. Results The serum levels of BAFF, gp130 and osteopontin were significantly higher in SPMS patients than in RRMS patients. The serum levels of BAFF correlated with age in both RRMS and SPMS patients. The serum levels of MMP-2 were significantly higher in RRMS patients than in SPMS patients and correlated with the number of past relapses. The serum levels of IL-32 were significantly higher in RRMS treatment-naïve patients than in RRMS patients treated with disease-modifying therapy. Discussion Significant differences were found in BAFF, gp130, MMP-2 and osteopontin levels between RRMS and SPMS patients. Serum IL-32 levels were statistically lower in RRMS patients treated with disease-modifying therapy than in treatment-naïve patients.

Serum Levels of IL-35, One of the Newest Members of Interleukin-12 Family of Cytokines, in Patients With Vitiligo.

Vitiligo is a chronic skin disorder in which immune dysregulation has been reported as one of the major etiopathological factors. Interleukin-12 (IL-12), IL-23 and IL-27 of IL-12 cytokine family were identified as critical cytokines in the pathogenesis of many autoimmune and inflammatory skin diseases including vitiligo. IL-35 is one of the newest member of IL-12 cytokine family. The purpose of our study was to examine serum IL-35 levels in addition to serum IL-12, IL-23, IL-27 levels in the vitiligo patients and control group, and to investigate the relationship of these cytokines with the characteristics of vitiligo. Serum IL-12, IL-23, IL-27 and IL-35 levels of 87 vitiligo patients and 70 healthy volunteers were analyzed using the enzyme-linked immunosorbent assay (ELISA). We compared the IL-12 cytokine family levels in the patient and control groups, and investigated the relationship of these levels with the characteristics of vitiligo. Patients had higher levels of IL-12 (31.2 versus 20.1, P < 0.001) and IL-35 (9.6 versus 8.1, P = 0.031). Patient and control groups had similar levels of IL-23 (P = 0.78) but were correlated with the Vitiligo Area Scoring Index (VASI) (P = 0.022, r = 0.35). Patients had lower levels of IL-27 (207.6 versus 258.7, P < 0.001). In addition, the levels of serum IL-27 were correlated negatively with the Vitiligo Disease Activity (VIDA), and positively with disease duration (P = 0.007, r = 0.30). Differences of serum levels between Vitiligo patients and healthy controls, significant relationships with the characteristics of vitiligo suggest that the IL-12 cytokine family may play a role in the pathogenesis of vitiligo.

P136 KL6 and IL-18 levels are negatively correlated with respiratory function tests and interstitial lung disease extent assessed on high-resolution computed tomography in patients with systemic sclerosis-related interstitial lung disease

Abstract Background/Aims Serum biomarkers have been suggested as indicators for pulmonary damage with clinical value in the diagnosis and prognosis of SSc-ILD. We aim to investigate the role of serum biomarkers (Krebs von den Lungen-6 KL-6, IL-18 and IL- 18BP) as potential biomarkers reflecting the severity of SSc-ILD as assessed through high-resolution computed tomography (HRCT) and pulmonary function tests (PFT). Methods A cross-sectional study including patients with SSc fulfilling the 2013 ACR/EULAR criteria was performed. Patients were classified according to disease duration and pulmonary involvement. All SSc patients underwent chest HRCT scans and pulmonary function test at baseline. Serum concentration of KL-6, IL8 and IL18BP were determined usingsandwich ELISA technique (solid phase sandwich Enzyme Linked-Immunosorbent Assay), with kits from MyBiosource for KL-6 and from Invitrogen for IL18 and IL18BP. A semiquantitative grade of ILD extent was evaluated through HRCT scan (grade 1, 0-20%; grade 2, &amp;gt;20%). Extensive lung disease was defined as &amp;gt; 20% of lung involvement on HRCT, and FVC &amp;lt;70% predicted and limited lung involvement as ≤ 20% of ILD involvement on HRCT,and an FVC ≥70% predicted. Results 74 patients were included, 27% were male, with a mean age of 57.5±15 years. 28 patients had ILD (38%). 64 % of patients had &amp;lt;20% of ILD extent classified through HRCT scan. SSc-ILD patients had elevated serum KL- 6 and IL-18 levels compared to patients without ILD (p = 0.003 and p = 0.04). A negative correlation between KL-6 levels and %FVC (β=-0.25, p 0.037) and %DLCO (β=-0.28, p 0.02) and between IL-18 levels and %FVC (β=-0.20, p 0.03) and %DLCO (β=-0.14, p 0.04) were found. Serum KL-6 and IL-18 levels successfully differentiated grades I and II (p = 0.028 and p = 0.021). Semiquantitative grades of ILD on the HRCT scan were significantly proportional to the KL-6 (p 0.01) and IL-18 (p = 0.03). A positive correlation between extensive lung disease and KL-6 (β = 0.61, p 0.007) but not with IL-18 was found. Conclusion Serum KL-6 levels and IL-18 were increased in patients with SSc-ILD and showed a positive correlation with ILD severity as measured using a semiquantitative HRCT grading scale and a negative correlation with PFT parameters. Disclosure C. Sieiro Santos: None. S. Calleja Antolín: None. J. de la Calle Lorenzo: None. E. Bollo de Miguel: None. E. Díez Álvarez: None.

The Role of Cannabinoid-1 Receptor Ligands in the Ovalbumin-Induced Mouse Model of Allergic Asthma: Is It Related to Transient Receptor Potential Vanilloid-1 Channels?

Objectives: The aim of this study was to investigate the role of cannabinoid (CB1) receptors on airway inflammation and hypersensitivity in allergic asthma and the potential interactions with TRPV1 channels. Materials and Methods: BALB/c mice were sensitized and provoked with ovalbumin to create a model of allergic asthma. CB1 selective agonist arachidonoyl 2'-chloroethylamide (ACEA) was administered intraperitoneally at doses of 0.5, 3, and 5 mg/kg. Receptor antagonism studies were performed utilizing selective CB1 antagonists AM251 at a dose of 3 mg/kg. TRPV1 channel was selectively blocked by capsazepine at a dose of 2.5 mg/kg. Penh values were recorded in vivo by a whole-body plethysmograph under methacholine challenge. Inflammatory cell count was performed in bronchoalveolar lavage fluid (BALF). Serum levels of proinflammatory cytokines were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Inflammation in the lung tissue was scored histopathologically. Statistical significance was determined using one-way analysis of variance or Kruskal-Wallis test and expressed as p<0.05. Results: In sensitized animals, provocation with inhaled ovalbumin increased Penh values, serum interleukin (IL)-4, IL-5, IL-13 levels, eosinophil, neutrophil, lymphocyte, macrophage counts in BALF, and inflammation in the lung tissue. ACEA applications did not significantly alter Penh values, BALF inflammatory cell levels, and histological changes related to inflammation in the lung tissue according to the disease group; however, only at a dose of 5 mg/kg, it reduced the levels of the inflammatory cytokine IL-4. AM251 decreased Penh values, eosinophil and neutrophil migration in BALF, and inflammation score of lung tissue compared with the disease group. Although BALF inflammatory cell levels and Penh values were higher in the AM251+ACEA group than in the AM251 group, the differences were insignificant. In the CPZ+ACEA group, Penh values were significantly higher, and serum IL-4 and IL-13 levels and BALF eosinophil counts were lower than that in the CPZ group. Conclusions: This study demonstrated an important role of the CB1 receptors in allergic asthma. CB1 antagonism reduced airway hyperresponsiveness and inflammation and showed immunomodulatory effects. The effect of the CB1 agonist ACEA on asthma does not appear to be related to TRPV1 channels.

Effects of electroacupuncture with "intestinal disease prescription" on NLRP3 inflammasome and intestinal mucosal barrier in rats with acute ulcerative colitis.

To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC. Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1β) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence. Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (P<0.01), increased DAI score and spleen index (P<0.01), elevated serum IL-18 and IL-1β levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (P<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (P<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (P<0.05), reduced DAI scores and spleen indexes (P<0.05), decreased serum IL-18 and IL-1β levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (P<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (P<0.05). There were no significant differences in the above indexes between the medication group and the EA group (P>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration. EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.

The role of FASL gene polymorphism (rs: 763110), its serum level and IL21 level with incidence of psoriasis in Iraqi patients

Psoriasis is a chronic, immune-mediated skin disease with systemic pro-inflammatory can defined by keratinocyte hyper proliferation. FASL gene cell surface death receptor which is important in apoptosis mediated by cytotoxic T cells and natural killer cells. The goals of current study is design to investigate genotyping of the FASL gene (Fas ligand gene) -844 T>C (rs:763110), evaluate its serum level and to estimate level of IL-21correlated with incidence of psoriasis in Iraqi patients. 100 blood samples collected from December 2022 to February 2023, blood samples split into two groups first 50 psoriasis patients (30 males and 20 females) with age range (17-66years) and second group 50 Apparently healthy as control group (24 males 26 females) with age range (20-60 years) visit the Al-Yarmouk Teaching Hospital’s Department of Dermatology in Iraq/Baghdad. (HRM–PCR) Technique was use for the investigation of gene polymorphism of the FASL gene (rs763110). While EIISA technique used to estimate serum level of each FASL gene and IL-21 in serum. The result of FASL gene polymorphism revealed that there are three genotype (TT),(TC),(CC). There was no significant difference, between (TC) and (CC) genotype In the FASLG -844 and between the psoriasis and control groups. Moreover there was correlation between genotyping and serum level for FASL (rs763110) gene in that (TC) genotype serum level show significant different from (CC) genotype serum level with p-value (P≤0.05) as well as the FASL serum level in patient which represent high significantly different between psoriasis patients when compared to the healthy controls with p-value (P≤0.01). While result of IL21 serum level in psoriasis patients revealed high significant different with p-value (P≤0.01) vs healthy control with high significant different in sever psoriatic patient vs mild and healthy control with p value (P≤0.01).

The serum levels of gasdermin D in uremic patients and its relationship with the prognosis: a prospective observational cohort study

Objective This study aimed to explore the serum levels of gasdermin D (GSDMD) in uremic (end-stage kidney disease, ESKD) patients and their correlation with vascular calcification (VC) and clinical results. Methods This prospective observational cohort study enrolled 213 ESKD patients who were undergoing regular maintenance hemodialysis (MHD) for > 3 months in our hospital from August 2019 to July 2022. The abdominal aortic calcification score (AACS) was used to assess the VC condition of patients with ESKD. Serum GSDMD, caspase-1, interleukin (IL)-6, IL-1β, IL-18 and C-reactive protein (CRP) levels were measured using enzyme-linked immunosorbent assay (ELISA). Demographic and clinical data were obtained. All patients were followed up for 1 year, and patients with major adverse cardiovascular events (MACE) were defined as having a poor prognosis. All data used SPSS 26.0 to statistical analyses. Results The serum total cholesterol (TC) levels of patients in the AACS > 4 group were significantly elevated compared with those in the AACS ≤ 4 group. In addition, ESKD patients with an AACS > 4 had significantly higher serum levels of GSDMD, caspase-1, IL-6, IL-18 and IL-1β. Moreover, Pearson’s analysis supported a positive correlation between GSDMD and caspase-1, IL-6, and IL-1β. In addition, we found that GSDMD levels were positively correlated with the clinical data (AACS scores and serum TC levels) of patients with ERSD. Additionally, ROC curves showed that the serum levels of GSDMD could be a potential predictive biomarker of moderate/severe VC and prognosis in patients with ESKD. Finally, the results of logistic regression indicated that GSDMD and AACS scores were risk factors for poor prognosis in patients with ESKD. Conclusion Serum GSDMD levels were remarkably elevated in patients with ESKD with moderate/severe calcification. In addition, serum levels of GSDMD could be a potential predictive biomarker of moderate/severe VC and prognosis in patients with ESKD.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1β (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1β, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

Interleukin-16 is increased in obesity and alters adipogenesis and inflammation in vitro.

Obesity is a chronic condition associated with low-grade inflammation mainly due to immune cell infiltration of white adipose tissue (WAT). WAT is distributed into two main depots: subcutaneous WAT (sWAT) and visceral WAT (vWAT), each with different biochemical features and metabolic roles. Proinflammatory cytokines including interleukin (IL)-16 are secreted by both adipocytes and infiltrated immune cells to upregulate inflammation. IL-16 has been widely studied in the peripheral proinflammatory immune response; however, little is known about its role in adipocytes in the context of obesity. We aimed to study the levels of IL-16 in WAT derived from sWAT and vWAT depots of humans with obesity and the role of this cytokine in palmitate-exposed 3T3-L1 adipocytes. The results demonstrated that IL-16 expression was higher in vWAT compared with sWAT in individuals with obesity. In addition, IL-16 serum levels were higher in patients with obesity compared with normal-weight individuals, increased at 6 months after bariatric surgery, and at 12 months after surgery decreased to levels similar to before the intervention. Our in vitro models showed that IL-16 could modulate markers of adipogenesis (Pref1), lipid metabolism (Plin1, Cd36, and Glut4), fibrosis (Hif1a, Col4a, Col6a, and Vegf), and inflammatory signaling (IL6) during adipogenesis and in mature adipocytes. In addition, lipid accumulation and glycerol release assays suggested lipolysis alteration. Our results suggest a potential role of IL-16 in adipogenesis, lipid and glucose homeostasis, fibrosis, and inflammation in an obesity context.

Aging considerations of cytokines (IL-18, IL-36α, IL-37, and IL-38) associated with rheumatoid arthritis

ABSTRACT The pro-inflammatory cytokines IL-18 and IL-36α and the anti-inflammatory cytokines IL-37 and IL-38 are proposed to have a pathophysiological role in rheumatoid arthritis (RA). However, this role has not been well investigated in relation to aging. In this study, serum IL-18, IL-36α, IL-37, and IL-38 levels were examined in 100 RA patients who were classified as young adults (<40 years) and elderly (>60 years). A similar classification was applied to 100 healthy controls. Serum IL-18, IL-36α, and IL-38 levels were significantly elevated in all RA patients compared to controls. When comparing young adult patients to elderly patients, only IL-18 showed significantly elevated levels in elderly patients. IL-18, IL-36α, and IL-38 showed excellent performance in differentiating between young adult patients and young adult controls, whereas in elderly patients, only IL-37 retained this performance. IL-18, IL-36α, and IL-38 were associated with an increased risk of RA in young adults, whereas in the elderly, only IL-37 was associated with an increased risk of RA. In conclusion, aging is an important factor proposed to influence the association pattern of IL-18, IL-36α, IL-37, and IL-38 in RA. These findings may reshape our understanding of the role of cytokines in the pathophysiology of RA.

Imbalance of Tfollicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data.

Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients. Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015-January 2020 were chosen for this study.The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson's Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems). Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples. The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.

Serum IL-31 is related to the severity and 3-month prognosis of patients with Intracerebral hemorrhage.

Interleukin (IL)-31/IL-33 axis has been proved to play an important role in the regulation of inflammation, and serum IL-33 was found to be a novel serum prognostic marker of intracerebral hemorrhage (ICH), while the value of serum IL-31 levels on prognosis in patients with ICH remains unknown. The present study was designed to study the value of serum IL-31 levels on prognosis in ICH patients. A total of 200 ICH patients and 50 healthy people were included in this study. We collected clinical data such as demographic data, laboratory data, admission disease scores and medical histories of these participants. We measured serum IL-31 levels using enzyme-linked immunosorbent assay, and assessed the prognosis of ICH patients 3 months after onset by mRS scale, and mRS > 2 was defined as a 3-month poor outcome. The level of IL-31 in ICH patients were significantly higher than that in healthy control people (211.91 ± 61.61 vs 167.64 ± 27.45 pg/mL, P < .001), and levels of IL-31 in ICH patients with 3-month good outcome were significantly lower than that in ICH patients with 3-month poor outcome (196.09 ± 50.84 vs 248.05 ± 41.41 pg/mL, P < .001). Results of correlation analysis suggested that the level of serum IL-31 was positively related to admission NIHSS score (r = 0.627, P < .001), hematoma volume (r = 0.352, P < .001), mRS score (r = 0.515, P < .001), high-density lipoprotein-cholesterol (r = 0.177, P = .012), serum C-reactive protein levels (r = 0.483, P < .001), and serum tumor necrosis factor α levels (r = 0.389, P < .001) in ICH patients, while the level of serum IL-31 was negatively related to the admission GCS score (r = -0.518, P < .001) and triglycerides (r = -0.147, P = .038). Results of multivariate regression analysis shows that serum IL-31 levels are an independent risk factor affecting NIHSS scores (OR = 1.023, 95% CI = 1.010-2.036) and 3-month prognosis (OR = 1.023, 95% CI = 0.982-1.747) in ICH patients. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of serum IL-31 level in evaluating the prognosis of ICH were 85.2% and 76.7%, respectively. A cutoff value of serum IL-31 level > 185.30 pg/mL may indicate a poor prognosis for ICH. Serum IL-31 levels on admission in ICH patients are associated with patient prognosis, and higher serum IL-31 levels are associated with a higher risk of poor prognosis in ICH patients.

Comparative evaluation of serum and gingival crevicular fluid levels of interleukin 21 in periodontally diseased and healthy patients.

Periodontitis is an inflammatory reaction to subgingival pathogenic microorganisms that causes gradual deterioration of the gingiva, periodontal ligament,and alveolar bone. Interleukin (IL)-21 is the most recently found member of type I cytokine family that is upregulated during inflammation. The current study aims to investigate the biological plausibility of IL-21 as a biomarker for chronic periodontitis. This cross-sectional clinico-biochemical investigation included 15 systemically healthy, 15 periodontally healthy, 15 chronic gingivitis, and 15 chronic periodontitis subjects aged 25 to 60 years. Following subject enrollment, gingival crevicular fluid (GCF) and blood samples were then taken from each subject. The concentration of IL-21 in all samples was determined using enzyme-linked immunosorbent assay (ELISA) kit. The data was examined using the Kruskal-Wallis test and the Spearman correlation test. Serum IL-21 levels in chronic periodontitis patients were substantially greater than in periodontally healthy individuals. GCF IL-21 levels were substantially greater in gingivitis and chronic periodontitis patients compared to periodontally healthy individuals. In terms of clinical indicators, serum IL-21 levels correlated significantly with bleeding index (BI) in the chronic periodontitis group. In chronic periodontitis group, disease severity as evaluated by probing pocket depth (PPD) and clinical attachment loss (CAL) did not correlate with serum or GCF IL-21 levels. According to the current study's findings, periodontally involved patients had higher IL-21 levels than periodontally healthy patients, suggesting it can be used as biomarker. Further studies with larger sample size can shed more light on the clinical advantage of IL-21 as a possible marker for disease activity and progression.

457 - A case of atypical Kawasaki Disease with elevated serum IL-18 and ferritin levels & potential IVIG resistance

457 - A case of atypical Kawasaki Disease with elevated serum IL-18 and ferritin levels & potential IVIG resistance

Low Serum IL-18 Levels May Predict the Effectiveness of Dupilumab in Severe Asthma.

Objective Dupilumab, a monoclonal antibody specific for the human interleukin (IL)-4 receptor α, is used to treat severe asthma, especially in patients with elevated blood eosinophil counts and fractional exhaled nitric oxide (FeNO). The therapeutic response to dupilumab is highly variable. In this study, we explored new serum biomarkers to accurately predict the effect of dupilumab and examine the effect of dupilumab based on changes in the clinical parameters and cytokine levels. Methods Seventeen patients with severe asthma treated with dupilumab were enrolled. Responders, defined as those with a >0.5-point decrease in the Asthma Control Questionnaire (ACQ) score after 6 months of treatment, were included. Results There were 10 responders and 7 non-responders. Serum type 2 cytokines were equivalent between responders and non-responders; the baseline serum IL-18 level was significantly lower in responders than in non-responders (responders, 194.9±51.0 pg/mL; non-responders, 323.4±122.7 pg/mL, p=0.013). The cut-off value of IL-18 at 230.5 pg/mL could be used to distinguish non-responders from responders (sensitivity 71.4, specificity 80.0, p=0.032). Conclusion A low baseline serum IL-18 level may be a useful predictor of an unfavorable response to dupilumab in terms of the ACQ-6.

Effect of levocetirizine hydrochloride on chronic urticaria and serum levels of total IgE and inflammatory factors

Purpose: To investigate the curative effect of levocetirizine hydrochloride tablets on chronic urticaria as well as its mediating effect on serum levels of total IgE and inflammatory factors.&#x0D; Methods: Ninety-two (92) patients with chronic urticaria, were randomly divided into control group (CG) and study group (SG). Patients in CG were treated with oral administration of desloratadine citrate tablets while SG patients received oral levocetirizine hydrochloride tablets. A comparative analysis was conducted between the two patient cohorts encompassing clinical therapeutic outcomes, symptom scoring, T lymphoid subset cell levels, serum total IgE concentrations, serum inflammatory factor levels, as well as adverse reactions.&#x0D; Results: Total treatment effectiveness was higher in SG (97.83 %) than in CG (82.61 %; p &lt; 0.05). After treatment, wheal duration, size and number as well as pruritus scores were markedly lower in SG than in CG, albeit non-significantly (p &gt; 0.05). The levels of CD3+ CD4+, and CD4+/CD8+ ratio in SG after treatment were significantly higher than those in CG (p &lt; 0.05). Furthermore, the serum IgE, IL-4 and IL-13 levels were significantly lower in SG than in CG, while the IFN-γ level was significantly higher (p &lt; 0.05).&#x0D; Conclusion: Levocetirizine hydrochloride tablets produce a significant clinical curative effect on chronic urticaria relative to desloratadine citrate tablets. It reduces the levels of inflammatory factors and mitigates immune dysfunction in patients by increasing the serum level of total IgE. Therefore, it is a potential candidate for further clinical investigations on a larger and more diverse population.

Circulating Interleukins-33 and -37 and Their Associations with Metabolic Syndrome in Arab Adults.

Interleukins (ILs) are a group of cytokines known to have immunomodulatory effects; they include ILs-33 and -37 whose emerging roles in the pathogenesis of metabolic syndrome (MetS) remain under investigated. In this study, we compared circulating IL-33 and IL-37 in Arab adults with and without MetS to determine its associations with MetS components. A total of 417 Saudi participants (151 males, 266 females; mean age ± SD 41.3 ± 9.0 years; mean body mass index ± SD 30.7 ± 6.3 kg/m2) were enrolled and screened for MetS using the ATP III criteria. Anthropometrics and fasting blood samples were taken for the assessment of fasting glucose and lipids. Circulating levels of IL-33 and IL-37 were measured using commercially available assays. The results showed higher levels of serum IL-33 and IL-37 in participants with MetS than those without (IL-33, 3.34 3.42 (2.3-3.9) vs. (1-3.9), p = 0.057; IL-37, 5.1 (2.2-8.3) vs. 2.9 (2.1-6.1), p = 0.01). Additionally, having elevated levels of IL-33 was a risk factor for hypertension, low HDL-c, and hypertriglyceridemia. A stratification of the participants according to sex showed that males had higher IL-33 levels than females [3.7 (3.0-4.1) vs. 3.15 (1.4-3.8), p < 0.001], while females had higher levels of IL-37 than males [3.01 (2.2-7.0) vs. 2.9 (2.1-5.6), p = 0.06]. In conclusion, the presence of MetS substantially alters the expression of ILs-33 and -37. IL-33 in particular can be potentially used as a therapeutic target to prevent MetS progression. Longitudinal and interventional studies are warranted to confirm present findings.

Serum Levels of IL-21, IL-23 and 8-hydroxy-2′-deoxyguanosine in Pediatric Severe Pneumonia Cases

Background: Pneumonia causes the majority of acute respiratory distress syndrome (ARDS) cases. The microbes that cause pneumonia are very diverse. In addition to DNA, RNA viruses, Gram-negative and Gram-positive bacteria cause two types of cytokine imbalances, anti-inflammatory and pro-inflammatory. It can also influence the progno-sis of sepsis and other infectious diseases. This study aims to search for 8-hydroxy-2'-deoxyguanosine (8-OHdG), IL-21, IL-23, and c-reactive protein (CRP) and compare cytokine levels. It is also to determine if Pediatric pneumonia patients CRP and cytokine levels correlate with results. Materials and Methods: In the study, blood was drawn from approximately 43 pediatric pneumonia patients and 43 healthy controls who came to the pediatric clinic to investigate serum IL-21, IL-23, 8-OHdG, and CRP levels. The levels of biomarkers were determined by ELISA method. Serum CRP levels were measured using the ATELLICA IM Analyzer. Results: Serum CRP, 8-OHdG, IL-21 and IL-23 levels were significantly higher in the pediatric pneumonia patient group than in the control group. Conclusions: Increased serum IL-21, IL-23, 8-OHdG and CRP expression in pediatric pneumonia patients is a poten-tial determinant suggesting that IL-21, IL-23-related cytokines may play a role in endothelial cell activation reported in patients. Increased 8-OHdG oxidative stress is more pronounced in patients without pediatric pneumonia while pro inflammatory cytokines are higher in pediatric pneumonia patients. However, it is used as a possible therapeu-tic target to reduce inflammation. Further study on the impact of these findings on comorbidities with larger num-ber test size is needed