IL-6 In Patients Research Articles

Treatment with Tezepelumab Reduces Serum Interleukin (IL)-5 and IL-13 in Patients with Severe, Uncontrolled Asthma to Levels Approaching those Observed in Healthy Individuals

In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations and inflammatory biomarker levels in adults with severe, uncontrolled asthma. This post hoc analysis evaluated changes in serum levels of IL-5 and IL-13 after tezepelumab treatment, relative to levels observed in healthy individuals.

Abstract PO082: Significance of Treg cells in pathogenesis of oral squamous cell carcinoma

Abstract Oral squamous cell carcinoma (OSCC) is one of the major cancers affecting in Asian countries. The main causative factor has been tobacco habit. It has been reported that immune dysfunction in these patients is one of the major factors for tumor growth and dissemination that affects disease free survival of the patients. We assessed the phenotypic and functional characteristics of Regulatory T (Treg) CD4+CD25+FoxP3+subsets in patients with OSCC by multicoloured flow cytometry. Subsequently we investigated the effects their inhibition via TDG on growth of OSCC cell lines in vitro. An increased (p<0.05) prevalence of Treg phenotypes (CD4+CD25+, CD4+FoxP3+, CD8+FoxP3+, CD4+CD25+FoxP3+) was observed in the peripheral circulation of OSCC patients that positively correlated with clinicopathological features. The increased frequency of CD4+CD8+CD25+FoxP3+, a unique T cell subset, CTLA4+, GITR+, NrP1+ and granzyme B+ (GzmB) Tregs also showed a significantly higher prevalence in OSCC patients. Functionally CD4+FoxP3+ Tregs showed skewed expression of IL2, IL10 and IL35 in patients as compared with the normal controls. Higher expression of TGFβ in tumor tissues suggests their dominant role in the up regulation of differentiation of Tregs from naive T cells in the tumor bearing host. Further, enhanced expression of CCR5 and CCR7 on Tregs with up regulation of their ligands (CCL5, CCL19 and CCL21) in tumor cells indicates efficient recruitment and trafficking of Tregs to the tumor site. Gal-1 expression was observed to be significantly higher in oral cancer patients. Treatment with βGBP showed growth promoting effects on Tregs and oral cancer cells. However, the treatment with its inhibitor TDG resulted in inhibition of Treg subsets and also decreased the frequency of IL10+ and IL35+ Tregs indicating its immunomodulatory effects. Hence, it seems reasonable to assume that modulation of functional dynamics of selective Treg subsets may be useful in enhancing anti tumor immunity and developing immunotherapeutic strategies for patients with oral squamous cell carcinoma. Citation Format: Sadhna Aggarwal, Suresh C. Sharma, Satya N. Das. Significance of Treg cells in pathogenesis of oral squamous cell carcinoma [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO082.

Role of IL-22 in persistent allergic airway diseases caused by house dust mite: a pilot study

BackgroundPersistent allergic airway diseases cause a great burden worldwide. Their pathogenesis is not clear enough. There is evidence that one of the recently described cytokine interleukin (IL) 22 may be involved in the pathogenesis of these diseases. Scientists argue if this cytokine acts as proinflammatory or anti-inflammatory agent. The aim of this study was to investigate IL-22 level in patients with persistent allergic airway diseases caused by house dust mite (HDM) in comparison with healthy individuals and to evaluate its relationship with IL-13 and IL-10 level, symptoms score and quality of life.MethodsPatients with persistent allergic rhinitis caused by HDM and having symptoms for at least 2 years with or without allergic asthma were involved into the study. Measurements of IL-22, IL-13 and IL-10 and in serum and nasal lavage was performed by ELISA. Questionnaires assessing symptoms severity and quality of life were used.ResultsA tendency was observed that IL-22 in serum and nasal lavage was higher in patients with allergic airway diseases compared to control group (14.86 pg/ml vs. 7.04 pg/ml and 2.67 pg/ml vs. 1.28 pg/ml, respectively). Positive statistically significant correlation was estimated between serum IL-22 and serum IL-10 (rs = 0.57, p < 0.01) and IL-13 (rs = 0.44, p < 0.05) level. Moreover, positive significant correlation was found between IL-22 in nasal lavage and IL-10 in nasal lavage (rs = 0.37, p < 0.05). There was a negative statistically significant correlation between serum IL-22 and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) (rs = − 0.42, p < 0.05).ConclusionOur study showed a possible anti-inflammatory effect of IL-22 in patients with persistent allergic airway diseases caused by HDM.

АНАЛІЗ ВЗАЄМОЗВ’ЯЗКУ РІВНІВ КІНЦЕВИХ ПРОДУКТІВ ГЛІКАЦІЇ З ЦИТОКІНОВИМ ПРОФІЛЕМ У ПАЦІЄНТІВ З АЛЕРГІЧНИМИ ХВОРОБАМИ НА ТЛІ ХРОНІЧНОЇ ЕПШТЕЙНА-БАРР ВІРУСНОЇ ІНФЕКЦІЇ

ANALYSIS OF THE CORRELATION BETWEEN ADVANCED GLYCATION END-PRODUCTS LEVELS AND THE CYTOKINE PROFILE IN PATIENTS WITH ALLERGIC DISEASES ASSOCIATED WITH CHRONIC EPSTEIN-BARR VIRAL INFECTION S. O. Zubchenko Danylo Halytsky Lviv National Medical University, Lviv, Ukraine Abstract. Advanced glycation end-products (AGEs) serve as densitometric markers of oxidative stress and inflammatory processes in many diseases and their complications. Objective: analysis of the correlation between AGEs and the cytokine profile in patients with allergic diseases associated with chronic Epstein-Barr viral infection (EBV-infection) in the active and latent phases. Object and methods. Determination and comparative analysis of AGEs levels and cytokines IL-17, IL-33, TNF-α in 66 patients aged (32.4 ± 7.5) years with allergic diseases associated with chronic EBV-infection in the active and latent phases and in EBV-seronegative patients with allergic diseases. Results. When determining AGEs by fluorescence spectroscopy in three groups of patients with allergic diseases, there was a reliably smaller number of AGEs than in healthy individuals. Presumably 12.3 % higher levels of IL-33 (p = 0.041) was determined in patients with active phase of EBV-infection compared to EBV-seronegative individuals, and in patients with latent phase of EBV-infection, the level of IL-17 was 3.54 times higher compared with EBVseronegative individuals (p = 0.011). It was determined that there is a reliable (p = 0.049) weak negative (r = -0.364) correlation between AGEs level and IL-33 in patients with allergic diseases associated with chronic EBV-infection in the active phase. It was investigated that no statistical difference between the levels of the proinflammatory cytokine TNF-α in the three groups was found. In patients with allergic diseases associated with chronic EBV-infection in the latent phase, a reliable (p = 0,032) weak negative (r = -0,364) correlation between AGEs and IL-17 was determined. Conclusions. Patients with allergic diseases compared to healthy individuals have lower levels of AGEs. AGEs play a significant pathogenetic role in the induction of allergic inflammatory process. AGEs accompanied by increased synthesis of IL-33 and IL-17 was more pronounced in patients with active phase EBV-infection, which was confirmed by clinical data. Key words: аdvanced glycation end-products, allergic diseases, chronic Epstein-Barr viral infection, cytokines. S. Zubchenko PhD, Associate Professor, Department of Clinical Immunology and Allergology Danylo Halytskyi Lviv National Medical University Pekarska street, 69, Lviv, Ukraine, 79010. Svitlanazu@gmail.com Аsthma and Allergy, 2021, 3, P. 30–35.

Salivary level of interleukin-17 in patients having atrophic and erosive oral lichen planus before and after treatment with topical steroids (A Controlled clinical trial)

Background: The present study was aimed to measure the salivary level of IL-17 in patients having atrophic and erosive Oral lichen planus lesions (OLP) and to evaluate the effect of topical corticosteroids used for treatment of erosive/atrophic oral lichen planus on the level of IL-17 in the saliva. Subjects and methods: The present study was performed on 40 subjects divided into 3 groups Group (I) Twenty patients diagnosed with erosive/atrophic OLP received topical steroid (triamcinolone acetonide0.1%) four times per day for four weeks. Group (II) Ten patients diagnosed with reticular OLP and Group (III) Ten patients with normal mucosa (healthy control Group). Salivary samples were collected before and after treatment in group (I) and once from subjects in group (II) and (III) for determination of IL-17 levels using enzyme-linked immunosorbent assay (ELISA). Results: The mean IL-17 levels in saliva of erosive/atrophic OLP group were statistically significantly higher before treatment with topical steroid than after treatment and both are statistically significantly higher than the reticular group and healthy control subjects. Also, the clinical score and pain visual analogue score values were statistically significantly higher in the erosive/atrophic group before treatment than after treatment. Conclusions: The salivary levels of IL-17 in erosive/atrophic OLP patients was higher than the reticular OLP patients and both are higher than the healthy control subjects, suggesting that IL-17 has a major role in the pathogenesis of OLP and its salivary level may be diagnostic for the severity of the condition of the erosive/atrophic OLP.

Serum Levels of IL-22in Patients with Oral Lichen Planus and Cutaneous Lichen Planus.

Statement of the Problem: Lichen planus disease is a chronic inflammatory disorder of mucosal and cutaneous tissues with yet unclear etiology and pathogenesis. Cytokines play an important role in the initiation, maintenance of inflammatory and intercellular crosstalk.Purpose: We assessed serum levels of IL-22 in patients with oral and cutaneous lichen planus and made comparison with healthy individuals.Materials and Method: In this case-control study, peripheral blood samples of 40 patients with lichen planus disease, included two groups of oral lichen planus (n=20) and cutaneous lichen planus (n=20) were compared with 32 healthy individuals in this case-control study. Serum samples were prepared from patients with lichen planus and IL-22 concentration was measured in each serum sample by using a commercial ELISA Kit. The obtained data were then analyzed using the Kruskal-Wallis (one-way ANOVA) test. Results: The IL-22 serum levels were significantly higher in patients with oral lichen planus compared to the healthy control group (p< 0.001). No statistically significant differences were observed in serum levels of IL-22 in cutaneous lichen planus patients compared to the controls (p= 0.183).Conclusion: Increased IL-22 serum levels in patients with oral lichen planus may play an important role in the pathogenesis of oral lichen planus. The administration of the recombinant or antagonist of IL-22 could be a new therapeutic opportunity in the treatment of oral lichen planus.

Variations in IL-22, IL-27 and IL-35 serum levels in untreated and treated hepatitis C patients.

Hepatitis C virus (HCV) is the leading cause of chronic liver diseases including hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. We aimed to assess serum levels of interleukin (IL)-22, IL-27 and IL-35 in patients with hepatitis C and healthy controls to investigate their possible relationship with viral genotypes and liver enzyme levels. A total of 30 newly diagnosed hepatitis C patients with no history of antiviral therapy and 30 healthy individuals participated in this study. Serum levels of IL-22, IL-27 and IL-35 were determined by ELISA in peripheral blood samples from patients prior to and following treament with pan-genotypic direct-acting anti-viral therapy. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were measured to determine any possible association between hepatic enzymes and cytokine serum levels concentrations. The results show elevated serum levels of of IL-35 in HCV-infected patients compared to treated cases and healthy controls, whereas there was no significant difference in IL-22 and IL-27 serum levels among the three groups. Additionally, the cytokine levels were not significantly correlated with certain genotypes and levels of liver enzymes. Our findings indicate a potential role for IL-35 in chronic HCV infection and therapeutic management of patients with hepatitis C infection.

An inter-correlated cytokine network identified at the center of cytokine storm predicted COVID-19 prognosis

The hyper-inflammatory response is thought to be a major cause of acute respiratory distress syndrome (ARDS) in patients with COVID-19. Although multiple cytokines are reportedly associated with disease severity, the key mediators of SARS-CoV-2 induced cytokine storm and their predictive values have not been fully elucidated. The present study analyzed maximal and early (within 10 days after disease onset) concentrations of 12-plex cytokines in plasma. We found consistently elevated plasma levels of IL-6, IL-8 and IL-5 in patients who were deceased compared with those who had mild/moderate or severe disease. The early plasma concentrations of IFN-a and IL-2 positively correlated with the length of the disease course. Moreover, correlation network analysis showed that IL-6, IL-8, and IL-5 located at the center of an inter-correlated cytokine network. These findings suggested that IL-8, IL-6, IL-5 might play central roles in cytokine storms associated with COVID-19 and that the early detection of multiple plasma cytokines might help to predict the prognosis of this disease.

Serum level of interleukin-22 in patients with cutaneous warts: A case-control study.

Warts are viral cutaneous infections caused by human papilloma virus (HPV), presented by verrucous growth over the skin surface. The immune response is considered to play a crucial role in HPV clearance. It depends on intact cellular immunity including natural killer (NK) cell and cytotoxic T cells. It has been clarified that T-helper (Th) 1 cytokines (interleukin (IL)-2, interferon-γ, and tumor necrosis factor-a) and IL-17 are involved in HPV clearance. IL-22 is one of IL-10 family of cytokines produced by NK cells, Th1, Th17, and Th22 cells. In the skin, IL-22 reduces keratinocyte cornification and enhances keratinocyte production of antimicrobial peptides. IL-22 overexpression has been demonstrated in various viral infections and skin inflammatory disorders. The aim of this study was to assess serum levels of IL-22 in patients with warts and its association with their different clinical characteristics. The study included 20 patients with warts and 20 control subjects. Serum concentration of IL-22 was measured by enzyme-linked immune sorbent assay. Serum levels of IL-22 were significantly higher in patients with warts than in control subjects (P<.001). The levels were significantly higher in patients with recurrent warts after prior treatment than in patients with first-time warts (P=.007). Moreover, a significant positive correlation was detected between serum levels of IL-22 and the number of warts (P=.017). Serum level of IL-22 was elevated in patients with warts. Thus, IL-22 may have a crucial role in the antiviral immune response against this infection.

Changes in the serum levels of anti-inflammatory interleukins in patients with atopic dermatitis after a course of phototherapy

BACKGROUND: The role of immunological disorders in the development of atopic dermatitis (AD) is currently beyond doubt.&#x0D; AIMS: Changes in the serum levels of IL-4, IL-10 and IL-13 in patients with atopic dermatitis (AD) after UV therapy combined with standard drug treatment have been studied.&#x0D; MATERIALS AND METHODS: The study included 80 patients with moderate to severe AD and 80 healthy volunteers. The patients with AD received a course of 311 nm UVB phototherapy combined with standard drug therapy. Serum IL-4, IL-10 and IL-13 levels were determined through enzyme-linked immunosorbent assay (ELISA).&#x0D; RESULTS: In the studied sample, patients with AD were found to have statistically significantly higher serum levels of IL-10 and IL-13 compared with healthy volunteers of the control group. Serum IL-10 level was 18.3 pg/ml in patients with AD and 13.2 pg/ml in those of the control group; the level of IL-13 was 15.8 pg/ml and 11.5 pg/ml, respectively; after the course of 311 nm UVB, serum IL-10 and IL-13 levels in patients with AD decreased (IL-10 by 27.8% and IL-13 by 12.5%). IL-4 values did not differ significantly in patients with AD and those in the control group, being 0.06 pg/ml and 0.05 pg/ml, respectively; after the course of phototherapy, serum IL-4 levels remained unchanged and were equal to 0.05 pg/ml.&#x0D; CONCLUSION: The results obtained confirm the assumptions about the significant role of IL-10 and IL-13 in the mechanisms of AD regulation and pathogenesis and demonstrate the anti-inflammatory efficacy of phototherapy (311 nm UVB) in patients with severe and moderate AD.

Expression and Significance of IL-9 and IL-6 in Patients with BCR-ABL- MPN

To investigate the expression of IL-9 and IL-6 in patients with BCR-ABL- bone marrow proli- ferative tumor (MPN), and to explore its role in the occurrence and development of MPN. A total of 71 newly diagnosis MPN patients treated in Tianjin Medical University General Hospital from 2018 to 2019 were selected, including 32 patients with polycythemia vera (PV) and 22 patients with primary thrombocytosis (ET), and 17 patients with primary myelofibrosis (PMF). Then 58 patients who retestine after treatment were selected as therapy group，and 20 healthy volunteers were recruited as control group. ELISA was used to detect the expression level of IL-6 and IL-9 in bone marrow supernatant, and the relative expression level of IL-6 and IL-9 mRNA in BMMNC was detected by real-time PCR. The proportion of Th9 cells in peripheral blood were detected by flow cytometry (FCM). The expression level of IL-6 mRNA and IL-9 mRNA of BMMNC and clinical indicators were analyzed, and the correlation between JAK2 gene mutation load and IL-9 level was further analyzed. The level of IL-6 in bone marrow supernatant and the expression of IL-6 mRNA in BMMNC were higher in the newly diagnosed group as compared with those in the treated group and the control group (P<0.001). The expression level of IL-9 in bone marrow supernatant and the expression of IL-9 mRNA in BMMNC were lower in the newly diagnosed group as compared with those in the treated group and the control group (P<0.05). The proportion of Th9 cells in peripheral blood was lower in the newly diagnosed group as compared with that in the treated group and the control group (P<0.001). The level of IL-6 in bone marrow supernatant and the expression of IL-6 mRNA in BMMNC in JAK2+ group were higher than those in JAK2- group (P<0.05). The expression level of IL-9 in bone marrow supernatant and the expression of IL-9 mRNA in BMMNC were lower in JAK2+ group as compared with those in JAK2- group (P<0.05). The expression of IL-6 and IL-9 in the patient group showed correlation with the number of lymphocytes (IL-6: r=-0.49, P<0.01; IL-9: r=0.53, P<0.001), and also related with Hb in PV patients (IL-6: r= 0.87, P<0.001; IL-9: r=-0.54, P<0.01), and platelets in ET patients (IL-6: r=0.64, P<0.05; IL-9: r=-0.46, P<0.05). The increased expression of IL-6 in MPN and hyperfunction may promote the progression of BCR-ABL- MPN disease. The expression of IL-9 in MPN decreases, and it negatively correlates with the mutation load of JAK2 gene, which may be related with the decrease of tumor environmental antitumor immune effect.

Cytokine profile and disease severity in patients with COVID-19

Cytokine dysregulation is the proposed mechanism for Coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the serum levels of interferon (IFN)-γ, interleukin (IL)-5, IL-8, Il-9, IL-17, TGF-β and IFN-γ in patients infected with SARS-CoV-2. The study was conducted between 63 adult patients with COVID‐19 and compared with 33 age and gender-matched healthy subjects as controls. The age range in both groups was 50–70 years. The patients were classified into mild group (33 patients) and severe group (30 patients). Serum samples were collected from all participants and tested for the cytokine levels by ELISA (enzyme-linked immunosorbent assay) method. Statistical analysis was performed using the one-way ANOVA. The mean serum levels of IFN-γ, TGF-β, IL-17 and IL-8 in the COVID‐19 patients were significantly higher than those observed in the control group. A comparison of between the mild and severe groups showed significant differences in TGF-β levels. The mean concentration of serum IL-5 and IL-9 in patients with COVID‐19 did not differ from those in the control group. Systemic IL-17 levels correlated positively and significantly with TGF-β in patients with COVID‐19. Th1 (IFN-γ), Treg (TGF-β), and Th17 (IL-17) cytokines concentration were increased in COVID-19 patients. Interferon-γ and IL-17 are involved in inducing and mediating proinflammatory responses. Our data suggest that TGF-β can be used as a predictive factor of disease severity in patients with COVID-19.

Reduced IL-35 in patients with immune thrombocytopenia.

: The occurrence and development of primary immune thrombocytopenia is closely related to autoimmune imbalanced. Thus, we conducted the current study to investigate the modulation of IL-35, a newly identified immunological self-tolerance factor on immune thrombocytopenic purpura (ITP). We were enrolled peripheral blood in 21 adult healthy volunteers, 21 active primary ITP patients and 16 ITP patients in remission. In the same period, bone marrow plasma was drawn from active primary ITP patients and 16 bone marrow donors. Enzyme-linked immunoassay was used to measure IL-35 levels in bone marrow mononuclear cells and peripheral blood mononuclear cells. Real-time quantitative PCR was used to study the mRNA expression levels of p35, Epstein-Barr virus-induced gene 3 in bone marrow mononuclear cells and peripheral blood mononuclear cells. Compared with the normal group, IL-35 levels of in ITP patients were decreased significantly. IL-35 level in bone marrow plasma was decreased more significantly than that in peripheral blood plasma at the same stage. The results showed that plasma IL-35 levels were significantly decreased in patients with active ITP compared with those of control individuals, and IL-35 levels in bone marrow plasma were decreased more significantly compared with those at the same stage. The pathogenesis of ITP is associated with decreased IL-35 levels. Further studies are needed to expand sample content and explore more in-depth investigate a possible role of IL-35 in the pathogenesis and course of ITP.

Increased IL-33 and IL-17 in Colorectal Carcinoma Patients with Severe Disease

Abstract Colorectal cancer (CRC) represents one of the most common cancers. It is frequently diagnosed at advanced stages, indicating on need for new diagnostic markers. The aim of this study was to determine systemic and fecal values of IL-17 and IL-33 in patients with CRC and the relationship with clinicopathological aspects of disease. The blood samples and feces liquid fraction of 50 patients with CRC were analyzed. Serum and fecal levels of IL-33 and IL-17 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Fecal levels of Il-33 and IL-17 were increased in CRC patients with poor tumor tissue differentiation. Serum IL-33 and fecal IL-17 were increased in patients with presence of lung/liver metastasis or peritoneal carcinomatosis, respectively, while enhanced fecal IL-33 was detected only in patients with peritoneal carcinomatosis. Positive correlation between IL-33 and IL-17 values in sera and feces, respectively was also observed. We believe that increased local values of IL-33 and IL-17, reflected trough higher fecal concentration, in CRC patients with poor tumor tissue differentiation and with presence of lung/liver metastasis or peritoneal carcinomatosis may be considered as a sign of the tumor’s malignant progression and, consequently, of a poor prognosis for patients.

From genes polymorphisms to mucosal expression of cytokines: evaluating IL-23/IL-17 axis in adult patients with gastritis.

Chronic inflammation is the typical sign of gastritis that may shift into gastric cancer. IL-17A and IL-17F as a novel inflammatory cytokines subset of CD4+Th play the main role in inflammation. A key cytokine receptor in the inflammatory IL-17/IL-23 axis, the interleukin 23 receptor (IL23R), may be related to gastritis. We evaluated the correspondence between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with TGF-β1, IL-6, IL-17, IL-21 and IL-23 mucosal mRNAs expression in uninfected H. Pylori (HP) chronic gastritis patients. Total RNA and genomic DNA were separated from gastric biopsies of 44 patients with gastritis. Subsequently, mucosal mRNAs expression of TGF-β1, IL-6, IL-17, IL-21 and IL-23 were assessed by real-time PCR. To polymorphisms determination of IL-17A G197A, IL-17F A7488G and IL-23R +2199A/C the PCR-RFLP was used in gastric biopsies. Results point that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms did not influence the mucosal expression of TGF-β1, IL-6, IL-17 and IL-21 (p> 0.05). In an opposite result, we don't find a correspondence between IL-17A G197A, IL-17F A7488G polymorphisms and mucosal expression of IL-23 (p> 0.05). In a contrary, we found a correlation between IL23R +2199A/C polymorphism and mucosal expression of IL-23 in patients with chronic gastritis (p< 0.05). These findings propose that IL23R +2199A/C polymorphism may change the mucosal expression of IL-23 pattern in patients with gastritis disease in the absence of HP, but to support the conclusion, more research may be required.

Association of salivary inflammatory biomarkers with primary Sjögren's syndrome.

Primary Sjogren's syndrome (pSS) is an autoimmune disease that leads to salivary and lacrimal gland dysfunction. The adaptive immune response associated with T helper-2 lymphocytes appears to be altered in these patients. Therefore, the objective of this study was to determine the salivary levels of interleukin (IL)-6, IL-5, and IL-4 in patients with pSS when compared to a healthy control (HC) group. The secondary objectives were to study whether ILs levels in pSS patients were associated with salivary flow, patient-reported outcomes (PROMs) for xerostomia and oral health quality of life (Oral Health Impact Profile-14 [OHIP-14]), pSS classification criteria and presence of extraglandular manifestations. A case-control study was conducted in 36 patients with pSS and 35 HCs. Cytokine levels were measured using high-sensitivity multiplex map human immunoassays. Unstimulated and stimulated whole saliva were collected and patients filled out questionnaires. The Mann-Whitney U test, chi-squared test, and Spearman correlation test were used. Interleukin-6 was significantly higher in pSS patients than in HCs (P=.0001). IL-6 was significantly higher in pSS patients with a positive salivary gland biopsy (P=.04), whole stimulated saliva hyposalivation (P=.02), and presence of musculoskeletal disorders (P=.03). There was a non-significant positive correlation between IL-6 levels and PROMs for xerostomia (r=.31; P=.06) and OHIP-14 (r=.07; P=.68) in pSS patients. Levels of IL-4 and IL-5 were not detected in both pSS and HCs patients. Salivary IL-6 levels are significantly associated with pSS patients, and therefore, it is hypothesized that this biomarker may be useful in the diagnosis and follow-up of this disease.

Plasma levels of IL-1β and IL-37 in patients with severe haemophilia.

ObjectiveHaemophilia A and B are disorders caused by the lack of clotting factors VIII and IX, respectively. Repeated bleeding into the same joint leads to haemophilic arthropathy (HA). Interleukin (IL)-1β is responsible for the pro-inflammatory response and IL-37 is induced by IL-1β stimuli to have an anti-inflammatory response and prevent uncontrolled inflammation and tissue damage. Our objective was to investigate plasma levels of IL-1β and IL-37 in patients with severe haemophilia with different severities of HA.MethodsPeripheral blood samples were collected from 14 patients with severe haemophilia A and 6 with severe haemophilia B, and 18 healthy individuals. Plasma levels of IL-1β and IL-37 were detected by immunoassay, and severity of HA was evaluated using the Pettersson scoring system. Plasma levels of IL-1β and IL-37 were analysed in patients with severe haemophilia grouped by Pettersson score and in healthy individuals.ResultsPlasma levels of IL-1β and IL-37 were significantly higher in patients with severe haemophilia compared with healthy individuals and significantly lower in those with moderate to severe HA than in those with no or mild HA.ConclusionsPlasma levels of IL-1β and IL-37 may be useful to track HA progression in patients with severe haemophilia.

A pro-inflammatory phenotype is associated with behavioural traits in children with Prader\u2013Willi syndrome

Several lines of evidence indicate that immune-inflammatory alterations are widely observed in various mental disorders. Genetic syndromes with high risk of psychiatric disorders may constitute a model for studies investigating this phenomenon. One of such genetically determined neurodevelopmental disorders is the Prader–Willi syndrome (PWS). Therefore, we aimed to profile a broad panel of immune-inflammatory markers in patients with PWS, taking into account co-morbid psychopathology. Participants were 20 children with PWS, and 20 healthy children matched for age, sex and body mass index. Behavioural symptoms and co-occurring psychopathological symptoms were assessed using the Child Behaviour Checklist (CBCL). We found significantly elevated levels of interleukin (IL)-1β and IL-13 in patients with PWS. There were significant positive correlations between the levels of IL-1β and scores of the following externalizing and internalizing CBCL domains: withdrawn/depressed, social problems, thought problems, attention problems, delinquent and aggressive behaviour in PWS children. Moreover, higher levels of IL-13 were associated with more severe psychopathology in terms of social and attention problems as well as delinquent and aggressive behaviour. Our findings imply that subclinical inflammation, observed as elevated IL-1β and IL-13 levels, appears only in PWS patients and is correlated to several psychopathological symptoms.

Associations of IL-18 and IL-9 expressions and gene polymorphisms with asthma.

To explore the associations of interleukin-18 (IL-18) and IL-9 gene polymorphisms with susceptibility to asthma, and to study the associations between IL-18 and IL-9 expression levels and polymorphisms. A total of 200 asthma patients in our hospital were collected as disease group, while 200 healthy people were taken as control group. The deoxyribonucleic acid (DNA) was extracted from peripheral blood and sent to the company for the detection of IL-18 and IL-9 gene polymorphisms via sequencing. The levels of serum IL-18 and IL-9 were determined using enzyme-linked immunosorbent assay (ELISA), and arterial blood gas analysis was performed for patients. The allele distributions at IL-18 gene loci rs189667 and rs360715 had no differences between control group and disease group. The allele distributions at IL-9 gene loci rs1859430 and rs2066758 were different between the two groups (p=0.001, p=0.022), among which the G allele frequency was the highest in disease group [245 (0.613)], and the T allele frequency was also the highest in disease group [240 (0.600)]. There was a difference in the genotype distribution at IL-9 gene locus rs1859430 between the two groups, and the GG genotype frequency in disease group [82 (0.410)] was significantly higher than that in control group (p=0.005). The CC genotype frequency at rs2066758 was significantly lower in disease group [27 (0.135), p=0.044]. In disease group, the frequency of heterozygous model CT (p=0.047) at IL-18 gene locus rs360715, and recessive model GA+AA (p=0.021) and heterozygous model GA (p=0.031) at IL-19 gene locus rs1859430 was significantly lower than that in control group. In disease group, the AC haplotype frequency at IL-18 gene loci rs189667 and rs360715 was evidently lower than that in control group (p=0.048). Disease group had evidently lower AT haplotype frequency (p=0.006) and evidently higher GT haplotype frequency (p=0.000) at IL-9 gene loci rs1859430 and rs2066758. Moreover, the level of serum IL-18 in patients with TT genotype at IL-18 gene locus rs360715 was higher than that in those with other genotypes in disease group (p<0.05), and the level of serum IL-9 in patients with AG genotype at IL-9 gene locus rs1859430 was also higher than that in those with other genotypes in disease group (p<0.05). There was a remarkable association between CT genotype at IL-18 gene locus rs360715 and partial pressure of oxygen (PaO2) (p=0.035), and between CC genotype at IL-9 gene locus rs2066758 and partial pressure of carbon dioxide (PaCO2) (p=0.041). The expression levels of serum IL-18 and IL-9 and their gene polymorphisms are significantly associated with asthma.

Different expression levels of interleukin-35 in asthma phenotypes

BackgroundInterleukin (IL)-35 is a newly discovered inhibitory cytokine which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It plays a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. Our study focuses on the sputum IL-35 level in patients and investigates different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes.ObjectiveWe aimed to determine the sputum IL-35 levels in asthmatic patients with clinical remission phenotypes and control subjects and to investigate possible correlations among lung function, age, sex, fractional exhaled nitric oxide (FeNO), and smoking history in these phenotypes.MethodsSputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction. Induced sputum was assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines were measured by ELISA and Cytometric Bead Array, respectively.ResultsSputum IL-35 (median (q1, q3)) levels showed no significant difference between asthma patients (4.89 ng/mL (2.97, 22.75)) and healthy controls (6.01 ng/mL (4.09, 30.47)). However, the sputum IL-35 level was significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL (2.80, 11.00)) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL (20.59, 65.06), p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL (3.10, 24.60), p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL (2.58, 52.45), p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors.ConclusionsSputum IL-35 is likely involved in different pathophysiological mechanisms of NA and EA and exerts different effects in asthma phenotypes.