Polimorfismo e concentração sérica da interleucina-10 em hanseníase

Detalhes bibliográficos
Autor(a) principal: Saunders, Ana Cecília de Brito
Data de Publicação: 2010
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/1753
Resumo: Leprosy is a world problem of health and Brazil has the second higher rates of new cases in the world. It is considered an endemic disease at Ceará and a total of 1,952 new cases were detected, reaching a detection rate of 22.8/100,000 inhabitants. The interaction between the M. leprae and different T cells stimulates the production of a Th1 or a Th2 pattern of cytokines, which are responsible for the different clinical forms of leprosy. Th1 cytokines (IL-2, IFN-γ and TNF-α) were found in tuberculoid skin lesions while Th2 cytokines (IL-4, IL-5 and IL-10) were found in lepromatoid lesions. Leprosy is influenced by many distinct factors, among them, genetic factors are the most studied at this moment. Cytokine genes seem to influence the interaction between the pathogen and the host and contribute to the development or not of the disease. The IL-10 is an antiinflammatory and immunomodulatory cytokine which has too much polymorphic promoter regions with microsatellites and SNPs. Different haplotypes are associated to distinct levels of cytokine production in vitro. Many studies reported associations between IL-10 polymorphisms and the risk or the protection against many diseases. However, the data reported have been contradictory and most of the associations between these polymorphisms and the production of IL-10 are showed in in vitro studies. The aim of this study was to evaluate how the promoter region polymorphisms of IL-10 influence the cytokine levels production in vivo, during the M. leprae infection. Serum levels of IL-10 were analyzed by ELISA in 181 individuals, 77 of them were leprosy cases, 74 household contacts and 30 healthy controls. Among them, 31 had IL-10 polymorphism typed in the case group, 33 in household contact group and 29 in healthy controls. Cases with polymorphism typed were stratified in low, medium and high levels of cytokine production. Differences in the IL-10 production were compared among leprosy cases (pauci and multibacillary), household contacts, healthy controls, genotypes and alleles distribution found in the groups. Kruskall-Wallis and Mann-Whitney tests were used to analyze mean values of IL-10 levels. No differences were observed between cases, contacts and controls (p=0.7450), pauci and multibacillary (p=0.7898), phenotypes of IL-10 production (low, medium or high) (p=0.4355). A significant difference in the IL-10 levels between cases and controls was found associated to the alleles -1082A,-819C and -592C (p<0.05) and between cases and contacts associated to the alleles -819C and -592C (p<0.05). No differences were found between contacts and controls (p>0.05). In conclusion, the -1082G>A, -819C>T and -592G>C IL-10 genotypes did not influence the IL-10 production or the M. leprae infection outcome. On the other hand, -1082A,-819C e -592C alleles determined a lower production of IL-10 in cases of leprosy. Keywords: Leprosy; Polymorphisms; IL-10; Serum levels; Contacts.
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spelling Polimorfismo e concentração sérica da interleucina-10 em hanseníaseSerum and polymorphism of the interleukin-10 in leprosyHanseníasePolimorfismo GenéticoLeprosy is a world problem of health and Brazil has the second higher rates of new cases in the world. It is considered an endemic disease at Ceará and a total of 1,952 new cases were detected, reaching a detection rate of 22.8/100,000 inhabitants. The interaction between the M. leprae and different T cells stimulates the production of a Th1 or a Th2 pattern of cytokines, which are responsible for the different clinical forms of leprosy. Th1 cytokines (IL-2, IFN-γ and TNF-α) were found in tuberculoid skin lesions while Th2 cytokines (IL-4, IL-5 and IL-10) were found in lepromatoid lesions. Leprosy is influenced by many distinct factors, among them, genetic factors are the most studied at this moment. Cytokine genes seem to influence the interaction between the pathogen and the host and contribute to the development or not of the disease. The IL-10 is an antiinflammatory and immunomodulatory cytokine which has too much polymorphic promoter regions with microsatellites and SNPs. Different haplotypes are associated to distinct levels of cytokine production in vitro. Many studies reported associations between IL-10 polymorphisms and the risk or the protection against many diseases. However, the data reported have been contradictory and most of the associations between these polymorphisms and the production of IL-10 are showed in in vitro studies. The aim of this study was to evaluate how the promoter region polymorphisms of IL-10 influence the cytokine levels production in vivo, during the M. leprae infection. Serum levels of IL-10 were analyzed by ELISA in 181 individuals, 77 of them were leprosy cases, 74 household contacts and 30 healthy controls. Among them, 31 had IL-10 polymorphism typed in the case group, 33 in household contact group and 29 in healthy controls. Cases with polymorphism typed were stratified in low, medium and high levels of cytokine production. Differences in the IL-10 production were compared among leprosy cases (pauci and multibacillary), household contacts, healthy controls, genotypes and alleles distribution found in the groups. Kruskall-Wallis and Mann-Whitney tests were used to analyze mean values of IL-10 levels. No differences were observed between cases, contacts and controls (p=0.7450), pauci and multibacillary (p=0.7898), phenotypes of IL-10 production (low, medium or high) (p=0.4355). A significant difference in the IL-10 levels between cases and controls was found associated to the alleles -1082A,-819C and -592C (p<0.05) and between cases and contacts associated to the alleles -819C and -592C (p<0.05). No differences were found between contacts and controls (p>0.05). In conclusion, the -1082G>A, -819C>T and -592G>C IL-10 genotypes did not influence the IL-10 production or the M. leprae infection outcome. On the other hand, -1082A,-819C e -592C alleles determined a lower production of IL-10 in cases of leprosy. Keywords: Leprosy; Polymorphisms; IL-10; Serum levels; Contacts.A hanseníase continua sendo um problema de saúde mundial, sendo o Brasil o segundo país em maior em número de casos novos. No Ceará a doença é considerada endêmica e em 2009 foram diagnosticados 1.952 casos novos, alcançando um coeficiente de detecção geral de 22,8/100.00 habitantes. A doença é causada pelo M. leprae, manifesta-se através de sinais e sintomas dermatoneurológicos e é transmitida de pessoa a pessoa através do convívio de indivíduos suscetíveis com doentes bacilíferos sem tratamento. A interação do M. leprae com os subtipos de células T produz citocinas do tipo Th1 e Th2, responsáveis pelas diferentes formas clínicas da doença. Padrões de citocinas Th1 (IL-2, IFN-γ e TNF-α) foram encontrados em lesões de pele das formas tuberculóides e padrões de citocinas Th2 (IL-4, IL-5 e IL-10) foram encontrados em lesões das formas virchovianas. A hanseníase é influenciada por vários fatores, sendo os genéticos os mais estudados no momento. Os genes das citocinas aparecem como fortes candidatos capazes de influenciar a interação patógeno- hospedeiro e favorecer ou não o desenvolvimento da doença. A IL-10 é uma citocina anti-inflamatória e imunomoduladora que possui regiões promotoras bastantes polimórficas, contendo regiões de microssatélites e SNPs que formam vários haplótipos que estão associados a diferentes níveis de produção de citocina in vitro. Vários estudos tentam reportar associações entre os polimorfismos de IL-10 e o risco ou proteção para diversas doenças. Contudo, os dados relatados tem sido contraditórios e a maioria das associações entre os polimorfismos e a produção dessa citocina são baseados em estudos in vitro. Dessa forma o presente estudo teve o objetivo de definir como os polimorfismos da região promotora da citocina afetam a produção in vivo frente à infecção pelo M. leprae. Foram quantificadas as concentrações séricas de IL-10 de 181 indivíduos, sendo 77 casos índices de hanseníase, 74 indivíduos contactantes e 30 controles saudáveis. Sendo que destes, 31 possuíam análise genotípica de IL-10 no grupo caso, 33 no grupo contactante e 29 no grupo controle. Os pacientes com análise genotípica foram estratificados em baixo, médio e alto produtor da citocina. As diferenças nos níveis da citocina foram comparadas entre os grupos dentro do espectro da hanseníase (paucibacilar e multibacilar), dos controles externos, dos controles internos, dos genótipos e alelos encontrados nos grupos. Foram realizados testes de Kruskall-Wallis e Mann-Whitney para análise das medianas de IL-10 em pg/mL. Não foi encontrada diferença significante entre os grupos caso, contactante e controle (p=0,7450), entre os indivíduos pauci e multibacilar (p=0,7898), entre os fenótipos de nível de produção de citocina (baixo, médio e alto) (p=0,4355). Foi encontrada diferença significante na produção de IL-10 entre os alelos -1082A,-819C e -592C do grupo caso em relação aos controles (p<0,05) e dos alelos -819C e -592C do grupo caso em relação aos contactantes (p<0,05). Não foi encontrada diferença significante entre os grupos contactante e controle (p>0,05). Em conclusão, os genótipos de IL-10, -1082G>A, -819C>T e -592G>C não influenciaram a produção e/ou o desfecho da infecção pelo M. leprae. Por outro lado, os alelos -1082A,-819C e -592C determinaram menor produção de IL-10 em indivíduos com hanseníase.Freitas , Max Victor CariocaSaunders, Ana Cecília de Brito2012-02-01T13:56:15Z2012-02-01T13:56:15Z2010info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfSAUNDERS, A. C. B. Polimorfismo e concentração sérica da interleucina-10 em hanseníase. 2010. 86 f. Dissertação (Mestrado em Patologia) - Polimorfismo e concentração sérica da interleucina-10 em hanseníase. 2010. 86 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina. Universidade Federal do Ceará, Fortaleza, 2010.Universidade Federal do Ceará, Fortaleza, 2010.http://www.repositorio.ufc.br/handle/riufc/1753porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-01-22T12:15:59Zoai:repositorio.ufc.br:riufc/1753Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-01-22T12:15:59Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Polimorfismo e concentração sérica da interleucina-10 em hanseníase
Serum and polymorphism of the interleukin-10 in leprosy
title Polimorfismo e concentração sérica da interleucina-10 em hanseníase
spellingShingle Polimorfismo e concentração sérica da interleucina-10 em hanseníase
Saunders, Ana Cecília de Brito
Hanseníase
Polimorfismo Genético
title_short Polimorfismo e concentração sérica da interleucina-10 em hanseníase
title_full Polimorfismo e concentração sérica da interleucina-10 em hanseníase
title_fullStr Polimorfismo e concentração sérica da interleucina-10 em hanseníase
title_full_unstemmed Polimorfismo e concentração sérica da interleucina-10 em hanseníase
title_sort Polimorfismo e concentração sérica da interleucina-10 em hanseníase
author Saunders, Ana Cecília de Brito
author_facet Saunders, Ana Cecília de Brito
author_role author
dc.contributor.none.fl_str_mv Freitas , Max Victor Carioca
dc.contributor.author.fl_str_mv Saunders, Ana Cecília de Brito
dc.subject.por.fl_str_mv Hanseníase
Polimorfismo Genético
topic Hanseníase
Polimorfismo Genético
description Leprosy is a world problem of health and Brazil has the second higher rates of new cases in the world. It is considered an endemic disease at Ceará and a total of 1,952 new cases were detected, reaching a detection rate of 22.8/100,000 inhabitants. The interaction between the M. leprae and different T cells stimulates the production of a Th1 or a Th2 pattern of cytokines, which are responsible for the different clinical forms of leprosy. Th1 cytokines (IL-2, IFN-γ and TNF-α) were found in tuberculoid skin lesions while Th2 cytokines (IL-4, IL-5 and IL-10) were found in lepromatoid lesions. Leprosy is influenced by many distinct factors, among them, genetic factors are the most studied at this moment. Cytokine genes seem to influence the interaction between the pathogen and the host and contribute to the development or not of the disease. The IL-10 is an antiinflammatory and immunomodulatory cytokine which has too much polymorphic promoter regions with microsatellites and SNPs. Different haplotypes are associated to distinct levels of cytokine production in vitro. Many studies reported associations between IL-10 polymorphisms and the risk or the protection against many diseases. However, the data reported have been contradictory and most of the associations between these polymorphisms and the production of IL-10 are showed in in vitro studies. The aim of this study was to evaluate how the promoter region polymorphisms of IL-10 influence the cytokine levels production in vivo, during the M. leprae infection. Serum levels of IL-10 were analyzed by ELISA in 181 individuals, 77 of them were leprosy cases, 74 household contacts and 30 healthy controls. Among them, 31 had IL-10 polymorphism typed in the case group, 33 in household contact group and 29 in healthy controls. Cases with polymorphism typed were stratified in low, medium and high levels of cytokine production. Differences in the IL-10 production were compared among leprosy cases (pauci and multibacillary), household contacts, healthy controls, genotypes and alleles distribution found in the groups. Kruskall-Wallis and Mann-Whitney tests were used to analyze mean values of IL-10 levels. No differences were observed between cases, contacts and controls (p=0.7450), pauci and multibacillary (p=0.7898), phenotypes of IL-10 production (low, medium or high) (p=0.4355). A significant difference in the IL-10 levels between cases and controls was found associated to the alleles -1082A,-819C and -592C (p<0.05) and between cases and contacts associated to the alleles -819C and -592C (p<0.05). No differences were found between contacts and controls (p>0.05). In conclusion, the -1082G>A, -819C>T and -592G>C IL-10 genotypes did not influence the IL-10 production or the M. leprae infection outcome. On the other hand, -1082A,-819C e -592C alleles determined a lower production of IL-10 in cases of leprosy. Keywords: Leprosy; Polymorphisms; IL-10; Serum levels; Contacts.
publishDate 2010
dc.date.none.fl_str_mv 2010
2012-02-01T13:56:15Z
2012-02-01T13:56:15Z
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dc.identifier.uri.fl_str_mv SAUNDERS, A. C. B. Polimorfismo e concentração sérica da interleucina-10 em hanseníase. 2010. 86 f. Dissertação (Mestrado em Patologia) - Polimorfismo e concentração sérica da interleucina-10 em hanseníase. 2010. 86 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina. Universidade Federal do Ceará, Fortaleza, 2010.Universidade Federal do Ceará, Fortaleza, 2010.
http://www.repositorio.ufc.br/handle/riufc/1753
identifier_str_mv SAUNDERS, A. C. B. Polimorfismo e concentração sérica da interleucina-10 em hanseníase. 2010. 86 f. Dissertação (Mestrado em Patologia) - Polimorfismo e concentração sérica da interleucina-10 em hanseníase. 2010. 86 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina. Universidade Federal do Ceará, Fortaleza, 2010.Universidade Federal do Ceará, Fortaleza, 2010.
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