Serum IL-5 Concentrations Research Articles

Evaluation of Interleukin-33, Interleukin-10 Levels in Rheumatoid Arthritis Patients on Long Term Therapy of Disease-Modifying Antirheumatic Drugs

Background: Rheumatoid arthritis is a prevalent, long-term, inflammatory autoimmune illness with a wide range of extra-articular symptoms that affects 0.24% of people worldwide. Finding new, RA-specific biomarkers may help in early diagnosis, treatment, and monitoring of the severity and response to therapy of the disease. Objective: Determining of (IL-33, IL-10) levels in blood of both patients on long term therapy, early diagnosis patients and healthy control groups by using ELISA technique. Method: A case-control study in the following study groups consisted of three group. Group 1 included (50) patients on medications (DMARDs), Group 2 included (50) early diagnosed patients without medication and group 3 included (50) healthy individuals. Result: The mean of serum IL-33 concentration was significantly difference in rheumatoid arthritis (157.15 ± 24.88) in treated patients, (513.11 ± 113.01), and in patients with early diagnosis (185.75 ± 30.71) compared to the healthy control group (P = 0.000). But Mean levels of serum IL-10 were 320.27 ± 37.82, 180.24 ± 12.68 and 493.80 ± 68.94 pg/ml in patients on treatment, early diagnosis patients and healthy control group respectively; the level was highly significant lower than in early diagnosis patients with RA in comparison with patient on treatment and healthy control and the IL-10 level in healthy control was highly significant higher than in Patients on treatment, but in Patients on treatment higher than in early diagnosis patients, (P = 0.000). Conclusion: IL-33 and IL-10 is regarded as a useful biomarker for the diagnosis of RA and for assessing the severity of the illness.

ST2 and IL-33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children.

The ST2/IL-33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL-33 polymorphisms with serum soluble (s) ST2 and IL-33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single-nucleotide polymorphisms (SNPs) in ST2 and IL-33 were determined, and associations of the SNP variants with serum levels of sST2 and IL-33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL-33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL-33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.

Serum alarmins and the risk of incident interstitial lung disease in rheumatoid arthritis.

To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Using serum collected at enrolment, three alarmins (IL-33, thymic stromal lymphopoietin [TSLP] and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score and anti-cyclic citrullinated antibody positivity. Of 2835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (hazard ratio [HR] 0.73 per log-fold increase; 95% CI: 0.57, 0.95; P = 0.018) and adjusted (HR 0.77; 95% CI: 0.59, 1.00; P = 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children

ObjectiveTo investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results(1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. ConclusionSerum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Relationship Between the Expression of LC3 (Microtubule-Associated Protein 1A/1B-Light Chain 3) in Nasal Mucosa and Serum IL-5 and IL-4 Concentrations in Allergic Rhinitis Mice.

To investigate the expression and correlation of autophagy-related microtubule-associated protein 1 light chain 3 beta LC3 and interleukin-5 IL-5 in allergic rhinitis AR. Fifty-six 7-week-old BALC/C mice were randomly divided into experimental group (n = 56) and control group (n = 8). The experimental group used Dermatophagoides farinae (Der f) for AR modeling, and control group used PBS solution. As the experimental group sampled at 6 time points, and 8 mice were sacrificed each time, while the control group was sacrificed 24 hours after the last dose. The contents of serum IL-4, IL-5, and dust mite specific IgE HDM-sIgE in mice were detected by enzyme-linked immunosorbent assay ELISA, and the morphological changes of nasal mucosa were detected by a hematoxylin-eosin H&E staining. The expression of LC3 in mouse nasal mucosa was detected by immunohistochemical staining. Spearman correlation coefficient was used to assess the relationship between LC3 and IL-5 levels. In AR mice modelled with dust mites, the serum levels of IL-4 and HDM-sIgE increased gradually, and the serum IL-5 concentration had a peak at the early intraperitoneal administration stage similar to that at the end of modelling. The LC3 level in nasal mucosa of AR mice modelled with dust mites increased gradually in the early stages, but stabilized in the later stages. The expression of LC3 level in nasal mucosa was a positively correlated ration between serum IL-5 level in AR mice. In the early stage of AR mice, the level of nasal mucosal autophagy and serum IL-5 levels were significantly increased and correlated, suggesting that nasal mucosal autophagy played a promoting role in the early stage of AR.

Tacrolimus improved the pregnancy outcomes of patients with refractory recurrent spontaneous abortion and immune bias disorders: a randomized controlled trial

To investigate the effect of tacrolimus treatment on refractory recurrent spontaneous abortion (RSA) patients with elevated serum IL-33/ST2 levels. This study was a randomized controlled trial (RCT) of refractory RSA patients with elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. A total of 149 women were enrolled, each of whom had had at least 3 serial miscarriages and was confirmed to have elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. These women were randomly divided into two groups. The tacrolimus group (n = 75) received basic therapy with the addition of tacrolimus (Prograf). Tacrolimus was administered at a dose of 0.05 ~ 0.1mg/kg/day from the end of the menstrual period to the beginning of the next menstrual period or to the 10th week of pregnancy. In contrast, basic therapy with the addition of placebo was given to the placebo group (n = 74). The main study outcome was the delivery of healthy newborns without deformities. A total of 60 (80.00%) patients in the tacrolimus group and 47 (63.51%) patients in the placebo group delivered healthy newborns [P = 0.03, odds ratio = 2.30; 95% confidence interval (1.10 ~ 4.81)]. The peripheral blood IL-33/ST2 levels and Th1/Th2 cell ratio of the tacrolimus group were much lower than those of the placebo group (P < 0.05). We validated our previous finding that serum IL-33 and sST2 concentrations are related to RSA. Immunosuppressive treatment with tacrolimus was demonstrated to be a promising method to treat refractory RSA with immune bias disorders.

Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome.

Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics.

POS0433 CAN INTERLEUKIN 33 (IL-33) BE CONSIDERED A VALUABLE BIOMARKER IN THE EARLY STAGES OF SYSTEMIC SCLEROSIS? ANALYSIS OF A MONOCENTRIC COHORT

Background:The ScS approach has changed considerably in recent years especially concerning the very early diagnosis of the disease (VEDOSS) at the time when the patient is still in an undifferentiated form (UCTD) at risk of developing SSc (1, 2). Of great value are different clinical, instrumental and laboratory findings, such as specific autoantibodies and Nailfold VideoCapillaroscopy (NVC), able to identify those cases progressing into overt SSc. IL-33 cytokine is known to exert pro-fibrotic effects through its membrane receptor ST2 on immune cells and myofibroblasts and recent studies suggest that it can be released following endothelial cell activation at the onset of SSc (3, 4).Objectives:Our aim has been to evaluate IL-33 serum levels in a monocentric cohort of VEDOSS patients, looking for the possible association with clinical phenotype and disease progression, focusing on the microvascular capillaroscopic changes.Methods:Fourty-seven VEDOSS patients underwent a complete clinical, instrumental and laboratory evaluation, including NVC and specific SSc autoantibodies. At baseline serum IL-33 levels were measured using an ELISA assay. In 32 of them we also had a second serum sample at a follow-up time of at least 24 months (range 24 to 96 months).Results:During the follow-up time, 17 patients were subsequently reclassified as having ScS whereas 30 remained VEDOSS. The “progressor” subjects positively correlated with the presence of anti-Topoisomerase I antibodies (p&gt;0,004). IL-33 concentrations had a median value of 427.2 pg/ml (IQR 967.9 pg/ml) at baseline and of 130.4 pg/ml (IQR 399 pg/ml) at the follow up, showing a statistically significant difference independently from the progression of the disease (p=0.03). Besides significantly higher levels were detected in those patients with more severe NVC changes, defined as “active” pattern (p&lt;0.05). Among the 47 VEDOSS patients, 12 started some kind of vascular therapy. In these patients serum IL-33 concentrations significantly lowered during the follow-up respect to those without any treatment (p&lt;0.03)Conclusion:The analysis of our data confirms previous report (5) on higher IL-33 serum levels in the very early stages of UCTD patients at risk for SSc, regardless of their progression in established SSc, although related to more severe microvascular NVC involvement. The lowering of IL-33 serum levels that we detected in the follow up of our patients, may be linked to the well-known endothelial changes during the progression of the SSc and seems also to be partially affected by treatments. Investigation on a greater number of patients are needed to better understand our findings.

Alarmins (IL-33, sST2, HMGB1, and S100B) as potential biomarkers for schizophrenia

There is growing evidence that immune/inflammatory processes are related to the etiology of schizophrenia. Danger-/damage-associated molecular patterns (DAMPs), also called alarmins, are recognized as inflammatory mediators that play an important role in the development of many infection-induced or sterile inflammatory diseases. The importance of DAMPs particles in various mental disorders is still not clear. Therefore, this study aimed to evaluate serum levels of the most promising alarmins (IL-33, sST2, HMGB1, and S100B), as potent schizophrenia biomarkers. Sixty-eight adult patients with chronic schizophrenia and twenty-nine healthy volunteers were included in this prospective study. Enzyme-linked immunosorbent assay (ELISA) was used to assess the serum concentration of IL-33, sST2, HMGB1, and S100B. We documented that the serum levels of IL-33 (p = 0.006), sST2 (p = 0.02), HMGB1 (p = 0.01), and S100B (p = 0.04) are significantly higher in patients with schizophrenia than in healthy subjects. In male, but not in female, patients with schizophrenia, we found a significant difference in the serum IL-33, sST2, and HMGB1 concentrations as compared to the healthy men. In both male and female patients with schizophrenia, there was no significant difference in the serum concentrations of S100B in comparison to control subjects. In patients with schizophrenia, no significant correlations were noticed neither between any studied alarmins and PANSS scores nor between CDSS scores. Given that all investigated alarmins participate in the course of the neuroinflammatory process, they might be considered as biomarkers of neuroinflammatory process underlying schizophrenia. Based on our observations, it seems that the most useful biological indicator of schizophrenia would be IL-33.

Therapeutic effects of recombinant SPLUNC1 on Mycoplasma ovipneumoniae-infected Argali hybrid sheep

Clinical therapeutic and immunoregulatory effects of recombinant SPLUNC1 protein (rSPLUNC1) were evaluated in Mycoplasma ovipneumoniae (Mo)-infected Argali hybrid sheep (AHS). Group A contained six Bashibai sheep (BS) and groups B–D contained six AHS each. All sheep were manually infected with Mo. Five days post-infection, rSPLUNC1 from BS and AHS was injected intratracheally into group C and D animals; physiological saline was administered to groups A and B. Serum IL-5, IL-6, and IL-9 were quantified by ELISA. After sacrificing the sheep, lung tissues were extracted for pathological examination. The qPCR was used to quantify Mo load in the lungs and evaluate therapeutic efficacy. Serum IL-5, IL-6, and IL-9 concentrations increased during early infection stages in all groups but were significantly lower in groups A, C, and D than in group B on days 14 and 21. On day 21, IL-5 concentrations were lower in group A than in groups C and D. IL-6 concentration in groups A, C, and D was significantly lower than that in group B, and that in groups C and D was significantly lower than that in group A. Mean mycoplasma pneumonia histopathology scores were significantly lower in groups C and D than in group B, and Mo load in group C and D lung tissue decreased significantly compared to that in group B. Intratracheal injection of rSPLUNC1 into Mo-infected sheep decreased the cytokine levels and alleviated clinical symptoms with no mortality. rSPLUNC1 had significant therapeutic effects on Mo-infected AHS and can regulate pro-inflammatory cytokines.

Study on Correlation between IL-33 serum level, IL-33 Gene Single Nucleotide Polymorphism and Rheumatoid Arthritis Susceptibility

Objective: To discuss the association between single nucleotide polymorphism (SNP) of rs1929992 in IL- 33gene and IL-33 serum level in rheumatoid arthritis (RA) susceptibility among Iraq population. Methods: A total of 50 samples were collected from 35 RA patients from November 2018 untill end of January 2019 together with 15 healthy physical examines in the same period were chosen as the subjects. The serum IL-33 levels measured by commercial ELISA kits . Erythrocyte sedimentation rate ,white blood cell were measured by standard laboratory techniques The RFLP-PCR reaction technique was used to detect the genotype distributions for rs1929992 in IL-33gene was carried out by using restriction enzyme. The frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility. Results: Serum IL-33concentration was significantly higher in patients with RA than in control groups. The homozygous genotype AA recorded higher frequency in RA patients (42.9%) than controls (6.7%) with a significant difference (P-value 0.001). Homozygote genotype GG frequency (45.7%) was a significant in patients compared to controls subject (33.3%) with a significant difference (P-value 0.016), and the genotype heterozygous GA frequency (11.4%) were non-significant in patients compared to controls (60.6%). The allele frequency for allele G was (51.4%)in patients compared with controls ( 63.3%) with a significant difference (P-value 0.022)while for the allele A was (48.6%) in patients compared with controls( 36.7% )with a significant difference (P- value 0.001). Conclusions: significant correlation between RA patients susceptibility and genotype AA and alleles at rs1929992in IL-33 gene is observed. From this study showed that the IL-33 levels were influenced by genetic variation at SNPs rs5743708and rs1929992, respectively.

Increased serum interleukin-33 concentrations predict worse prognosis of aneurysmal subarachnoid hemorrhage

BackgroundInterleukin-33 (IL-33) is an inflammatory biomarker. We elucidated the relationship between serum IL-33 concentrations, severity and prognosis in aneurysmal subarachnoid hemorrhage (aSAH). MethodsWe prospectively recruited 175 controls and 175 aSAH patients. Serum IL-33 concentrations were gauged using an enzyme-linked immunosorbent assay. Clinical and radiological severity was assessed by World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale respectively. Poor outcome was defined as Glasgow Outcome Scale score of 1–3. ResultsSerum IL-33 concentrations were significantly higher in patients than in controls. IL-33 concentrations were significantly increased with increasing WFNS scores, modified Fisher scores and serum C-reactive protein concentrations. Serum IL-33 emerged as an independent predictor for 6-month mortality and poor outcome. Under receiver operating characteristic curve, the prognostic predictive ability of serum IL-33 was equivalent to those of WFNS scores and modified Fisher scores. Moreover, serum IL-33 significantly improved the prognostic predictive performance of WFNS scores and modified Fisher scores. ConclusionsHigh serum IL-33 concentrations have close relation to the inflammation, severity and poor outcome in aSAH, indicating IL-33 might have the potential to be an inflammatory biomarker for assessing severity and reflecting prognosis of aSAH.

Innate immune response reflects disease activity in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease characterized by allergic granulomatosis, necrotizing vasculitis, and peripheral blood eosinophilia. Interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and type 2 innate lymphoid cells (ILC2) are involved in the innate and type 2 immune responses in EGPA. However, the relationships among these molecules and the mechanisms underlying the development of EGPA remain unknown. We investigated the relationships among peripheral blood eosinophil count, serum IL-33 and TSLP concentration, and peripheral blood ILC2 count in patients with EGPA, chronic eosinophilic pneumonia (CEP), or bronchial asthma (BA). We recruited 86 patients with EGPA in three groups (remission, relapse, and onset), 25 patients with CEP at active or inactive stages of disease, and 11 patients with BA. In patients with EGPA, CEP, or BA, serum IL-33, sST2, and TSLP concentrations were determined using ELISA and peripheral blood ILC2 counts (as Lin-1- CD127+ CRTH2+ cells) were determined using flow cytometry. Peripheral blood eosinophil count or ILC2 count, and serum sST2 or TSLP concentration were higher in patients with EGPA at onset than in those with EGPA at relapse or remission, or in those with BA or CEP. Serum IL-33 concentration was higher in patients with EGPA at relapse than in those with EGPA at onset or remission, or in those with BA or CEP. In a logistic regression model, EGPA disease activity was correlated with serum IL-33 concentration and peripheral blood ILC2 count, but not daily systemic and inhaled corticosteroid dose or immunosuppressant use. Eosinophil count was correlated with peripheral blood ILC2 count and serum TSLP concentration, but not serum IL-33 concentration. Increased peripheral blood ILC2 count and serum IL-33 concentration were associated with disease activity in EGPA. Increases in serum IL-33 concentration may indicate the presence of active vasculitis rather than peripheral or tissue eosinophilia.

Stage classification of IgG4-related dacryoadenitis and sialadenitis by the serum cytokine environment

Objectives: Patients with immunoglobulin-G4 related disease (IgG4-RD) diagnosed according to the comprehensive diagnostic criteria (CDC) show varied therapeutic responses and prognoses. We assumed that there are clinical stages in IgG4-RD and have verified it using serum cytokine levels in the groups classified by lesion distribution.Methods: Definite IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) cases were divided according to the CDC for IgG4-RD into 11 cases with focal type and 30 cases with systemic type. The levels of serum interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, IL-15, IL-21, interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and monocyte chemotactic protein (MCP)-1 were measured in healthy controls, allergic patients, probable IgG4-RD cases, and focal and systemic type cases. The cytokine environment was analyzed in each group. The 52 definite IgG4-RD cases were next classified into four groups with cluster analysis in terms of therapeutic responses and prognosis. The relationships between each cytokine level and therapeutic responses were also analyzed.Results: Both serum IL-5 and IFN-α concentrations were very low in healthy controls, but they increased in the allergic cases, probable cases, and focal and systemic type cases. The level of serum IL-5 was significantly higher in definite cases than in healthy controls. The serum IL-5 level was also significantly increased in the groups with a poor prognosis than in the good prognosis group.Conclusion: These results suggest that there are clinical stages in IgG4-RD, and serum IL-5 play roles in the pathogenesis of IgG4-RD.

Low Variability in Peak Expiratory Flow Predicts Successful Inhaled Corticosteroid Step-Down in Adults with Asthma

The prognosis for patients beyond 1 year after reduction of their inhaled corticosteroid (ICS) dose remains unknown. Predictive factors that can be evaluated before the initiation of asthma treatment or at ICS dose reduction are unknown. We prospectively studied 223 patients in 6 hospitals in the National Hospital Organization of Japan during the 36 months after 50% reduction of their daily ICS dose. All patients recorded their morning and evening peak expiratory flows (PEFs) in their diaries. Lung function, bronchial hyperresponsiveness, fractional nitric oxide levels, number of eosinophils in sputum, and serum IgE levels were measured in most patients. Serum levels of IL-10, IL-33, and thymic stromal lymphopoietin before ICS dose reduction were measured in all patients. During the 36-month study period, asthma control was retained in 127 (59.6%) of the 213 enrolled patients who underwent ICS dose reduction. Multivariate logistic regression analysis revealed that, at the initiation of dose reduction, the factors most predictive of maintenance of asthma control after ICS dose reduction were a low serum IL-33 level (P < .01), low PEF variability over 1 week (P= .014), childhood onset of asthma (at age <10 years) (P= .03), and high serum IL-10 level (P= .035). We demonstrated that low PEF variability over 1 week, high serum IL-10 level, and low serum IL-33 concentration were useful factors for predicting that an adult's asthma will remain in control for months to years after a 50% reduction in the daily ICS dose.

IL-33 deficiency slows cancer growth but does not protect against cisplatin-induced AKI in mice with cancer.

The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in a 4-wk model of cisplatin-induced AKI in mice with cancer was determined. Mice were injected subcutaneously with murine lung cancer cells. Ten days later, cisplatin (10 mg·kg-¹·wk-¹) was administered weekly for 4 wk. The increase in kidney IL-33 preceded the AKI and tubular injury, suggesting that IL-33 may play a causative role. However, the increase in serum creatinine, blood urea nitrogen, serum neutrophil gelatinase-associated lipoprotein, acute tubular necrosis, and apoptosis scores in the kidney in cisplatin-induced AKI was the same in wild-type and IL-33-deficient mice. There was an increase in kidney expression of pro-inflammatory cytokines CXCL1 and TNF-α, known mediators of cisplatin-induced AKI, in IL-33-deficient mice. Surprisingly, tumor weight, tumor volume, and tumor growth were significantly decreased in IL-33-deficient mice, and the effect of cisplatin on tumors was enhanced in IL-33-deficient mice. As serum IL-33 was increased in cisplatin-induced AKI in mice, it was determined whether serum IL-33 is an early biomarker of AKI in patients undergoing cardiac surgery. Immediate postoperative serum IL-33 concentrations were higher in matched AKI cases compared with non-AKI controls. In conclusion, even though the cancer grows slower in IL-33-deficient mice, the data that IL-33 deficiency does not protect against AKI in a clinically relevant model suggest that IL-33 inhibition may not be useful to attenuate AKI in patients with cancer. However, serum IL-33 may serve as a biomarker of AKI.

Investigating the role of IL-33 in the pathogenesis of Behçet’s Disease

Objectives: Behçet’s disease (BD) is an inflammatory disease, characterized by oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations. Increased release of several cytokines may play a role in the inflammatory stages of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role in inflammation. We analyzed serum IL-33 concentration in BD patients to assess its possible role in the pathophysiology of this disease.Methods: The study included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18 matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked immunosorbent assay (ELISA).Results: The mean serum IL-33 levels were 4.84 ± 2.81 pg/ml in the BD patients (6.16 ± 2.94 pg/ml in the active stage and 2.86 ± 0.54 pg/ml in the inactive stage) and 2.88 ± 0.42 pg/ml in the healthy controls. Serum IL-33 levels were significantly higher in patients with BD compared with the healthy controls (p < 0.01). In active Behçet patients with arthritis the mean serum IL-33 level was higher but this finding was not statistically significant (p = 0.122).Conclusion: IL-33 may play a significant role of in the pathogenesis of BD.

Inflammation elevated IL-33 originating from the lung mediates inflammation in acute lung injury

Excessive inflammatory reactions occur with acute respiratory distress syndrome (ARDS), however, the underlying mechanisms of ARDS remain incompletely understood. Here we investigated whether interleukin (IL)-33 was elevated in ARDS patients. Serum samples were obtained from 14 ARDS patients and 24 control healthy volunteers. ELISA was used to measure the concentrations of IL-33. Besides, we established pulmonary ARDS and extrapulmonary ARDS models in mice, and serum and lung tissue samples were collected for analyses. The results showed that serum IL-33 concentrations were significantly higher in pulmonary ARDS patients compared to controls. Also, the levels of IFN-γ and IL-2 were positively correlated with IL-33 levels. We also showed that there were increased IL-33 levels in both the serum and lungs in the pulmonary ARDS model. This was not the case, however, in the extrapulmonary ARDS model. Pulmonary inflammation and injury in the pulmonary ARDS model was reduced with IL-33 neutralizing antibody treatment.

Aberrant Expression of Novel Cytokine IL-38 and Regulatory T Lymphocytes in Childhood Asthma.

We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4+CD25+CD134+ T lymphocytes as well as CD4+CD25highFoxP3+ and CD4+CD25highCD127− Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. Serum and supernatant cytokines/chemokines were determined by multiplex assay. Serum IL-38, IL-5, IL-17, IL-6, interferon-γ, periostin, IL-1β and IL-13 concentrations were significantly higher in asthmatic patients with or without steroid treatment than those in controls (all p < 0.05). The percentages of both CD4+CD25highFoxP3+ and CD4+CD25highCD127− Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p < 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients with high level (>40 ng/mL) of periostin (p < 0.05). Although the comparable mRNA levels of IL-38 and its receptor IL-36R were found between patients and controls, the mRNA level of IL-38 positively correlated with IL-36R and negatively correlated with IL-10 in all asthmatic patients (both p < 0.05). The percentage of CD4+CD25+CD134+ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in controls (p < 0.05). This cross-sectional study demonstrated that the overexpression of circulating IL-38 may play a role in the immunopathogenesis in asthma.

Investigating the Role of IL-33 in the Pathogenesis of Familial Mediterranean Fever

Abstract Familial mediterranean fever (FMF) is an autosomal recessive genetic disorder familial disease with inflammatory reactions of serosal membranes characterized by recurrent episodes of abdominal chest and joint pain, and fever. During the acute attacts, increased several proinflammatory cytokines have been described. IL-33 is a member of the IL-1 cytokine superfamily. It has been reported that IL-33 plays an important role in inflammation and homeostasis. Here, we analyzed serum IL-33 concentration in patients with FMF to assess its possible role in the pathophysiology of this disease. Material and method In this study, 58 patients with FMF (21 female, 37 male; mean age 27.8 ± 5.2 years, mean disease duration 8.2 ± 3,7 years) and 22 healthy controls (10 female, 12 male, mean age 26,5 ± 5,9 years) were included. Serum IL-33 levels were measured by ELISA. Results The mean serum IL-33 levels were 3,88 ± 2,25 pg/ml in patients with FMF and 2,89 ± 0.48 pg/ml in the healthy controls. The mean levels of serum IL-33 were 5,48 ± 2,13 pg/ml in active stage and 2,27 ± 0,36 pg/ml in inactive stage. According to these results; serum IL-33 levels were significantly higher in patients with FMF compared with healthy controls (p&amp;lt;0.01). In addition, Serum IL-33 levels were significantly higher in active stage compared to in inactive stages and controls (p&amp;lt;0.0001 and p&amp;lt;0.0001). In the inactive patients with FMF, serum IL-33 concentrations were found to be lower compared to healthy controls (p&amp;lt;0.05). In active FMF patients, the mean serum IL-33 level was correlated with arthritis (p&amp;lt;0.05). Conclusion The high levels of serum IL-33, in active patients with FMF suggest that IL-33 may play a significant role of in the pathogenesis of FMF.