Cytokine: X最新文献

{"title":"Using CRISPR to enhance T cell effector function for therapeutic applications","authors":"Julian J. Freen-van Heeren","doi":"10.1016/j.cytox.2020.100049","DOIUrl":"10.1016/j.cytox.2020.100049","url":null,"abstract":"<div><p>T cells are critical to fight pathogenic microbes and combat malignantly transformed cells in the fight against cancer. To exert their effector function, T cells produce effector molecules, such as the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Tumors possess many inhibitory mechanisms that dampen T cell effector function, limiting the secretion of cytotoxic molecules. As a result, the control and elimination of tumors is impaired. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for cancer immunotherapy. Recently, the first-in-patient clinical trial was successfully performed with CRISPR/Cas9-modified human T cell therapy. In this review, a brief overview of currently available techniques is provided, and recent advances in T cell genomic engineering for the enhancement of T cell effector function for therapeutic purposes are discussed.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"3 1","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25388145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-human primates and Leishmania immunity","authors":"Sonia André ,&nbsp;Vasco Rodrigues ,&nbsp;Morgane Picard ,&nbsp;Ricardo Silvestre ,&nbsp;Jérôme Estaquier","doi":"10.1016/j.cytox.2020.100038","DOIUrl":"10.1016/j.cytox.2020.100038","url":null,"abstract":"<div><p>In the context of infectious diseases, non-human primates (NHP) provide the best animal models of human diseases due to the close phylogenetic relationship and the similar physiology and anatomical systems. Herein, we summarized the contribution of NHP models for understanding the immunity to leishmaniases, which are a group of diseases caused by infection with protozoan parasites of the genus <em>Leishmania</em> and classified as one of the neglected tropical diseases.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25388141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines and splenic remodelling during Leishmania donovani infection","authors":"Marcela Montes de Oca ,&nbsp;Christian R. Engwerda ,&nbsp;Paul M. Kaye","doi":"10.1016/j.cytox.2020.100036","DOIUrl":"10.1016/j.cytox.2020.100036","url":null,"abstract":"<div><p>Visceral leishmaniasis (VL) causes extensive splenic pathology that contributes to dysfunctional immune responses, in part through displacement and destruction of cell populations involved in maintaining splenic structural integrity. The expression of pro and anti-inflammatory cytokines and chemokines is crucial in orchestrating the delicate balance that exists between host resistance and tissue pathology. In an effort to restore homeostatic balance to the local microenvironment, remodelling of the splenic architecture occurs in a compartmentalised manner to retain some level of functionality, despite persistent inflammatory pressures. Animal models of VL as well as human studies have significantly contributed to our understanding of the architectural changes that occur in the spleen during VL. Here, we review the role of cytokines in mediating microarchitectural changes associated with the development of splenomegaly during VL.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25383815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An IL-6-IL-8 score derived from principal component analysis is predictive of adverse outcome in acute myocardial infarction","authors":"Gisela A. Kristono ,&nbsp;Ana S. Holley ,&nbsp;Kathryn E. Hally ,&nbsp;Morgane M. Brunton-O'Sullivan ,&nbsp;Bijia Shi ,&nbsp;Scott A. Harding ,&nbsp;Peter D. Larsen","doi":"10.1016/j.cytox.2020.100037","DOIUrl":"10.1016/j.cytox.2020.100037","url":null,"abstract":"<div><h3>Introduction</h3><p>Many studies have shown that elevated biomarkers of inflammation following acute myocardial infarction (AMI) are associated with major adverse cardiovascular events (MACE). However, the optimal way of measuring the complex inflammatory response following AMI has not been determined. In this study we explore the use of principal component analysis (PCA) utilising multiple inflammatory cytokines to generate a combined cytokine score that may be predictive of MACE post-AMI.</p></div><div><h3>Methods</h3><p>Thirteen inflammatory cytokines were measured in plasma of 317 AMI patients, drawn 48–72 h following symptom onset. Patients were followed-up for one year to determine the incidence of MACE. PCA was used to generate a combined score using six cytokines that were detectable in the majority of patients (IL-1β, -6, -8, and -10; MCP-1; and RANTES), and using a subset of cytokines that were associated with MACE on univariate analysis. Multivariate models using baseline characteristics, elevated individual cytokines and PCA-derived scores determined independent predictors of MACE.</p></div><div><h3>Results</h3><p>IL-6 and IL-8 were significantly associated with MACE on univariate analysis and were combined using PCA into an IL-6-IL-8 score. The combined cytokine score and IL-6-IL-8 PCA-derived score were both significantly associated with MACE on univariate analysis. In multivariate models IL-6-IL-8 scores (OR = 2.77, p = 0.007) and IL-6 levels (OR = 2.18, p = 0.035) were found to be independent predictors of MACE.</p></div><div><h3>Conclusion</h3><p>An IL-6-IL-8 score derived from PCA was found to independently predict MACE at one year and was a stronger predictor than any individual cytokine, which suggests this may be an appropriate strategy to quantify inflammation post-AMI. Further investigation is required to determine the optimal set of cytokines to measure in this context.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25383816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of the first reference antibody panel for qualification and validation of cytokine release assay platforms – Report of an international collaborative study","authors":"Sandrine Vessillier ,&nbsp;Madeline Fort ,&nbsp;Lynn O'Donnell ,&nbsp;Heather Hinton ,&nbsp;Kimberly Nadwodny ,&nbsp;Joseph Piccotti ,&nbsp;Peter Rigsby ,&nbsp;Karin Staflin ,&nbsp;Richard Stebbings ,&nbsp;Divya Mekala ,&nbsp;Aarron Willingham ,&nbsp;Babette Wolf ,&nbsp;participants of the study","doi":"10.1016/j.cytox.2020.100042","DOIUrl":"10.1016/j.cytox.2020.100042","url":null,"abstract":"<div><p>Immunomodulatory therapeutics such as monoclonal antibodies (mAb) carry an inherent risk of undesired immune reactions. One such risk is cytokine release syndrome (CRS), a rapid systemic inflammatory response characterized by the secretion of pro-inflammatory cytokines from immune cells. It is crucial for patient safety to correctly identify potential risk of CRS prior to first-in-human dose administration. For this purpose, a variety of in vitro cytokine release assays (CRA) are routinely used as part of the preclinical safety assessment of novel therapeutic mAbs. One of the challenges for the development and comparison of CRA performance is the lack of availability of standard positive and negative control mAbs for use in assay qualification. To address this issue, the National Institute for Biological Standards and Control (NIBSC) developed a reference panel of lyophilised mAbs known to induce CRS in the clinic: human anti-CD52, mouse anti-CD3 and human superagonistic (SA) anti-CD28 mAb manufactured according to the respective published sequences of Campath-1H® (alemtuzumab, IgG1) , Orthoclone OKT-3® (muromonab, IgG2a) and TGN1412 (theralizumab, IgG4), as well as three isotype matched negative controls (human IgG1, mouse IgG2a and human IgG4, respectively).<!--> <!-->The relative capacity of these control mAbs to stimulate the release of IFN-γ, IL-2, TNF-α and IL-6 in vitro was evaluated in eleven laboratories in an international collaborative study mediated through the HESI Immuno-safety Technical Committee Cytokine Release Assay Working Group. Participants tested the NIBSC mAbs in a variety of CRA platforms established at each institution. This paper presents the results from the centralised cytokine quantification on all the plasma/supernatants corresponding to the stimulation of immune cells in the different CRA platforms by a single concentration of each mAb. Each positive control mAb induced significant cytokine release in most of the tested CRA platforms. There was a high inter-laboratory variability in the levels of cytokines produced, but similar patterns of response were observed across laboratories that replicated the cytokine release patterns previously published for the respective clinical therapeutic mAbs. Therefore, the positive and negative mAbs are suitable as a reference panel for the qualification and validation of CRAs, comparison of different CRA platforms (e.g. solid vs aqueous phase), and intra- and inter-laboratory comparison of CRA performance. Thus, the use of this panel of positive and negative control mAbs will increase the confidence in the robustness of a CRA platform to identify a potential CRS risk for novel immunomodulatory therapeutic candidates.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38831248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism","authors":"Christian Bogdan","doi":"10.1016/j.cytox.2020.100041","DOIUrl":"10.1016/j.cytox.2020.100041","url":null,"abstract":"<div><p><em>Leishmania</em> are protozoan parasites that predominantly reside in myeloid cells within their mammalian hosts. Monocytes and macrophages play a central role in the pathogenesis of all forms of leishmaniasis, including cutaneous and visceral leishmaniasis. The present review will highlight the diverse roles of macrophages in leishmaniasis as initial replicative niche, antimicrobial effectors, immunoregulators and as safe hideaway for parasites persisting after clinical cure. These multiplex activities are either ascribed to defined subpopulations of macrophages (e.g., Ly6C^highCCR2⁺ inflammatory monocytes/monocyte-derived dendritic cells) or result from different activation statuses of tissue macrophages (e.g., macrophages carrying markers of of classical [M1] or alternative activation [M2]). The latter are shaped by immune- and stromal cell-derived cytokines (e.g., IFN-γ, IL-4, IL-10, TGF-β), micro milieu factors (e.g., hypoxia, tonicity, amino acid availability), host cell-derived enzymes, secretory products and metabolites (e.g., heme oxygenase-1, arginase 1, indoleamine 2,3-dioxygenase, NOS2/NO, NOX2/ROS, lipids) as well as by parasite products (e.g., leishmanolysin/gp63, lipophosphoglycan). Exciting avenues of current research address the transcriptional, epigenetic and translational reprogramming of macrophages in a <em>Leishmania</em> species- and tissue context-dependent manner.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25388143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral immunity in leishmaniasis – Prevention or promotion of parasite growth?","authors":"Ricardo Goncalves ,&nbsp;Stephen M. Christensen ,&nbsp;David M. Mosser","doi":"10.1016/j.cytox.2020.100046","DOIUrl":"10.1016/j.cytox.2020.100046","url":null,"abstract":"<div><p>Leishmaniasis can present as a “spectrum” of clinical outcomes. There is evidence that these divergent clinical outcomes are attributable to genetic differences in the human host <span>[1]</span> as well the species of infecting parasite <span>[2]</span>. The spectrum of disease has largely been described by defining the polar opposites of T cell immune responses. In the mouse model, a T_H1 immune response is associated with low numbers of <em>Leishmania</em> parasites in lesions, whereas a T_H2 immune response has been associated with unrestricted parasite growth. In the present work, we revisit leishmaniasis and seek to better define the clinical spectrum as a function of divergent humoral immune responses. We describe examples in human, canine, and even some murine models of leishmaniasis that reveal a direct correlation between high anti-parasite antibody responses and unrestricted parasite growth. Therefore, we propose that the spectral nature of this disease may be due to quantitative and qualitative differences in the antibodies that are produced during disease. In human visceral leishmaniasis, a decrease in anti-parasite antibody levels may actually predict disease resolution. Thus, rather than defining this disease as a simple T_H1/T_H2 dichotomy, we propose that clinical leishmaniasis depends on the degree of humoral immunity, with high IgG predicting parasite persistence. These observations have obvious implications for vaccine development in leishmaniasis, and they may extend to other diseases caused by intracellular pathogens.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25388142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocilizumab for severe COVID-19 related illness – A community academic medical center experience","authors":"Kapil S Meleveedu ,&nbsp;John Miskovsky ,&nbsp;Joseph Meharg ,&nbsp;Abd Abdelrahman ,&nbsp;Richa Tandon ,&nbsp;Ashley E. Moody ,&nbsp;Priscilla Dasilva ,&nbsp;Gabrielle Masse ,&nbsp;Jason LaPorte ,&nbsp;Abdul Saied Calvino ,&nbsp;Greg Allen ,&nbsp;Rabih El-Bizri ,&nbsp;Todd Roberts ,&nbsp;Vincent Armenio ,&nbsp;Steven C. Katz","doi":"10.1016/j.cytox.2020.100035","DOIUrl":"10.1016/j.cytox.2020.100035","url":null,"abstract":"<div><p>The SARS-CoV-2 virus responsible for the COVID-19 pandemic can result in severe or fatal disease in a subset of infected patients. While the pathogenesis of severe COVID-19 disease has yet to be fully elucidated, an overexuberant and harmful immune response to the SARS-CoV-2 virus may be a pivotal aspect of critical illness in this patient population. The inflammatory cytokine, IL-6, has been found to be consistently elevated in severely ill COVID-19 patients, prompting speculation that IL-6 is an important driver of the pathologic process. The inappropriately elevated levels of inflammatory cytokines in COVID-19 patients is similar to cytokine release syndrome (CRS) observed in cell therapy patients. We sought to describe outcomes in a series of severely ill patients with COVID-19 CRS following treatment with anti-IL-6/IL-6-Receptor (anti-IL-6/IL-6-R) therapy, including tocilizumab or siltuximab. At our academic community medical center, we formed a multi-disciplinary committee for selecting severely ill COVID-19 patients for therapy with anti-IL-6 or IL-6-R agents. Key selection criteria included evidence of hyperinflammation, most notably elevated levels of C-reactive protein (CRP) and ferritin, and an increasing oxygen requirement. By the data cutoff point, we treated 31 patients with anti-IL-6/IL-6-R agents including 12 who had already been intubated. Overall, 27 (87%) patients are alive and 24 (77%) have been discharged from the hospital. Clinical responses to anti-IL-6/IL-6-R therapy were accompanied by significant decreases in temperature, oxygen requirement, CRP, IL-6, and IL-10 levels. Based on these data, we believe anti-IL-6/IL-6-R therapy can be effective in managing early CRS related to COVID-19 disease. Further study of anti-IL-6/IL-6-R therapy alone and in combination with other classes of therapeutics is warranted and trials are underway.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38449530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the unsolved paradoxes of cytokine families in host resistance and susceptibility to Leishmania infection","authors":"Bernard Ong'ondo Osero ,&nbsp;Raphael Taiwo Aruleba ,&nbsp;Frank Brombacher ,&nbsp;Ramona Hurdayal","doi":"10.1016/j.cytox.2020.100043","DOIUrl":"https://doi.org/10.1016/j.cytox.2020.100043","url":null,"abstract":"<div><p>Leishmaniasis is a neglected disease caused by protozoan parasites of the genus <em>Leishmania</em>. Successful clearance of <em>Leishmania</em> relies on a robust human immune response and various cytokines have been implicated in resistance and susceptibility to <em>Leishmania</em> infection. Accordingly, various immunotherapeutic approaches involving cytokines and cytokine receptors are being considered as novel avenues of treatment given the limited efficacy of current anti-leishmanial drugs. These approaches target canonical T helper (Th)1/Type 1 cytokines as intended mediators of host-protection to infection whilst concomitantly suppressing Th2/Type 2 cytokines and their anticipated disease-promoting roles. However, the use of cytokine and cytokine receptor gene-deficient mice over the years has challenged this simplistic view of Th1/Type 1-mediated resistance and Th2/Type 2-mediated susceptibility. Indeed, contribution to susceptibility vs resistance is only a partial consequence to cytokine action as the overall response is multi-faceted due to the pleiotropic, redundant, antagonistic and synergistic action of cytokines and interactions with immune cells in the diseased state. Notably, while the responses of certain cytokines are selectively host-protective or characteristic disease-enhancers, some ligands exert a response depending on the parasite-species initiating infection. Paradoxically, others play dual or contradictory roles in different <em>Leishmania</em> immunopathologies. Hence, cytokines in disease is an unsolved paradox and a comprehensive knowledge of cytokine interplay is important to guide the development of novel immunotherapeutics against leishmaniasis. In this review, we characterize various cytokine families in persistence and clearance of the <em>Leishmania</em> parasite and particularly elucidate unsolved cytokine puzzles in leishmaniasis based on information acquired from “gain of knowledge by loss of function” studies in cytokine and cytokine receptor gene-deficient mice.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 4","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91963409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New variants in NLRP3 inflammasome genes increase risk for asthma and Blomia tropicalis-induced allergy in a Brazilian population","authors":"Gerson de A. Queiroz ,&nbsp;Raimon R. da Silva ,&nbsp;Anaque de O. Pires ,&nbsp;Ryan dos S. Costa ,&nbsp;Neuza M. Alcântara-Neves ,&nbsp;Thiago M. da Silva ,&nbsp;Mauricio L. Barreto ,&nbsp;Sergio C. Oliveira ,&nbsp;Camila A. Figueirêdo","doi":"10.1016/j.cytox.2020.100032","DOIUrl":"10.1016/j.cytox.2020.100032","url":null,"abstract":"<div><p>Atopic asthma is a chronic lung disease of lower airways caused mainly due to action of T-helper (Th) 2 type cytokines, eosinophilic inflammation, mucus hypersecretion and airway remodelling. Interleukin (IL)-33 increases type 2 immunity polarization in airway playing critical role in eosinophilic asthma. On the other hand, NLRP3 inflammasome activation results in the release of caspase-1 (Casp-1) which, in its turn, promotes IL-33 inactivation. Recent studies have shown associations between <em>NLRP3</em> variants and inflammatory diseases. However, no study with genes in NLRP3 inflammassome route has been conducted so far with asthma and atopy in any population to date. Blood samples were collected from 1246 asthmatic and non-asthmatic children. Associations were tested for single nucleotide polymorphism (SNP)s in <em>NLRP3</em> and <em>CASP1</em> with asthma and markers of atopy and in cultures stimulated with <em>Blomia tropicalis</em> (Bt) mite crude extract. The T allele of rs4925648 (<em>NLRP3)</em> was associated with increased asthma risk (OR 1.50, P = 0.005). In addition, the T allele of rs12130711 polymorphism, whithin the same gene, acted as a protector factor for asthma (OR 0.78, P = 0.038). On the other hand, the C allele of rs4378247 <em>NLRP3</em> variant was associated with lower levels of IL-13 production when peripheral blood cells were stimulated with Bt (OR 0.39, P = 4E-04). In addition, the greater the number of risk alleles in <em>IL33</em>/<em>NLRP3</em>/<em>CASP1</em> route the greater was the risk for asthma. The T allele of rs7925706 <em>CASP1</em> variant was also associated with increased risk for asthma (OR 1.47, P = 0.008). In addition, this same allele increased the eosinophil counts in blood (mm3) in asthmatic individuals compared with non-asthmatic (P = 0.0004). These results suggest that <em>NLRP3</em> and <em>CASP1</em> polymorphisms may be associated with susceptibility for asthma and markers of atopy in our population.</p></div>","PeriodicalId":37028,"journal":{"name":"Cytokine: X","volume":"2 3","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cytox.2020.100032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38554976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}