Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Farhad Rezaei, Saied Bokaie, Farzaneh Tofighi Zavareh, Fatemeh Kiaee, Ali N Kamali, Gholamreza Azizi, Abbas Mirshafiey
{"title":"白细胞介素-1β和白细胞介素-6在常见变异性免疫缺陷中的作用及其与B细胞亚型的关系以及对肺炎-23疫苗的应答","authors":"Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Farhad Rezaei, Saied Bokaie, Farzaneh Tofighi Zavareh, Fatemeh Kiaee, Ali N Kamali, Gholamreza Azizi, Abbas Mirshafiey","doi":"10.1684/ecn.2019.0435","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.</p><p><strong>Method: </strong>Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine.</p><p><strong>Results: </strong>Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21<sup>low</sup> expressing B cells were found.</p><p><strong>Conclusion: </strong>Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21<sup>low</sup> expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"30 4","pages":"123-129"},"PeriodicalIF":2.2000,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1684/ecn.2019.0435","citationCount":"2","resultStr":"{\"title\":\"Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine.\",\"authors\":\"Laleh Sharifi, Asghar Aghamohammadi, Nima Rezaei, Reza Yazdani, Farhad Rezaei, Saied Bokaie, Farzaneh Tofighi Zavareh, Fatemeh Kiaee, Ali N Kamali, Gholamreza Azizi, Abbas Mirshafiey\",\"doi\":\"10.1684/ecn.2019.0435\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.</p><p><strong>Method: </strong>Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine.</p><p><strong>Results: </strong>Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21<sup>low</sup> expressing B cells were found.</p><p><strong>Conclusion: </strong>Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21<sup>low</sup> expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.</p>\",\"PeriodicalId\":11749,\"journal\":{\"name\":\"European cytokine network\",\"volume\":\"30 4\",\"pages\":\"123-129\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2019-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1684/ecn.2019.0435\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European cytokine network\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1684/ecn.2019.0435\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European cytokine network","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1684/ecn.2019.0435","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine.
Introduction: Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.
Method: Peripheral blood mononuclear cells of CIVD patients were stimulated with and without TLR2 and TLR4 agonist and specific inhibitors including lipopolysaccharide (LPS), lipoteichoic (LTA), and OxPAPC. The levels of IL-1β and IL-6 were assessed by ELISA in different treatment groups. Finally, association of cytokines levels was assessed among different subtypes of B cells and types of response to Pneumovax-23 vaccine.
Results: Secretion of IL-6 and IL-1β was significantly diminished in CVID patients (p = 0.015 and p = 0.019), but ligand engagement of TLR2 and TLR4 leads to significant increase in IL-6 and IL-1β production. IL-6 was significantly lower in Pneumovax-23 hypo responder patients (p = 0.05) and significant correlations between the concentration of IL-6 and the number of switched memory and CD21low expressing B cells were found.
Conclusion: Secretion of IL-6 and IL-1β is abolished in CVID patients. However, TLR2 and TLR4 are hyper responsive to stimulation with their cognate ligands resulting in the secretion of higher levels of proinflammatory cytokines. This characteristic of CVID TLRs leads to an improvement of cytokine secretion compared to baseline levels. Also, our novel findings about the association concentrations of serum IL-6 and the frequency of with switched memory and CD21low expressing B cells as well as the poor response to Pneumovax-23 should be substantiated by the use of a higher sample size in future studies.
期刊介绍：
The journal that brings together all areas of work involving cytokines.
European Cytokine Network is an electronic journal that publishes original articles and abstracts every quarter to provide an essential bridge between researchers and clinicians with an interest in this cutting-edge field.
The journal has become a must-read for specialists in the field thanks to its swift publication and international circulation.
The journal is referenced in several databases, including Medline, which is testament to its scientific quality.
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