Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

Erika Muller Ramalho Zenha, Carlos Gustavo Wambier, Ana Lúcia Novelino, Thiago Antônio Moretti de Andrade, Maria Aparecida Nunes Ferreira, Marco Andrey Cipriani Frade, Norma Tiraboschi FossDivision of Dermatology, Ribeirão Preto Medical School, S&a...

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Autores principales: Zenha EM, Wambier CG, Novelino AL, Andrade TA, Ferreira MA, Frade MA, Foss NT
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:d4fc7c5415494bb586c64eb0b54fbecd2021-12-02T04:54:33ZClinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study1178-7031https://doaj.org/article/d4fc7c5415494bb586c64eb0b54fbecd2012-12-01T00:00:00Zhttp://www.dovepress.com/clinical-and-immunological-evaluation-after-bcg-id-vaccine-in-leprosy--a11779https://doaj.org/toc/1178-7031Erika Muller Ramalho Zenha, Carlos Gustavo Wambier, Ana Lúcia Novelino, Thiago Antônio Moretti de Andrade, Maria Aparecida Nunes Ferreira, Marco Andrey Cipriani Frade, Norma Tiraboschi FossDivision of Dermatology, Ribeirão Preto Medical School, São Paulo University, São Paulo, BrazilIntroduction: The use of bacillus Calmette–Guérin (BCG) has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity.Methods: To investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB) and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL)-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id). Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A), lipopolysccharides (LPS), or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF)-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment. Results: The results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017) in MB patients and of IL-17 (P = 0.008) and IFN-γ (P = 0.037) in paucibacillary patients. Immunohistochemical staining, especially for TNF-α, was more intense in biopsies of MB leprosy patients taken after BCG-id administration, probably for induction of innate human immunity. The clinical evaluation suggests that BCG-id is able to induce a more effective therapeutic response, with reduction of the number and the intensity of leprosy reactions. Conclusion: These results suggest that BCG-id induces activation of the initial phase of immunocellular activity: innate human immunity (increase in TNF-α, IL-12 and macrophage activation). Therefore, we conclude that the use of BCG-id could be indicated as an adjuvant to multidrug therapy in treatment of leprosy patients.Keywords: leprosy, immunology, BCGZenha EMWambier CGNovelino ALAndrade TAFerreira MAFrade MAFoss NTDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2012, Iss default, Pp 125-135 (2012)
institution DOAJ
collection DOAJ
language EN
topic Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Zenha EM
Wambier CG
Novelino AL
Andrade TA
Ferreira MA
Frade MA
Foss NT
Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study
description Erika Muller Ramalho Zenha, Carlos Gustavo Wambier, Ana Lúcia Novelino, Thiago Antônio Moretti de Andrade, Maria Aparecida Nunes Ferreira, Marco Andrey Cipriani Frade, Norma Tiraboschi FossDivision of Dermatology, Ribeirão Preto Medical School, São Paulo University, São Paulo, BrazilIntroduction: The use of bacillus Calmette–Guérin (BCG) has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity.Methods: To investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB) and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL)-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id). Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A), lipopolysccharides (LPS), or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF)-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment. Results: The results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017) in MB patients and of IL-17 (P = 0.008) and IFN-γ (P = 0.037) in paucibacillary patients. Immunohistochemical staining, especially for TNF-α, was more intense in biopsies of MB leprosy patients taken after BCG-id administration, probably for induction of innate human immunity. The clinical evaluation suggests that BCG-id is able to induce a more effective therapeutic response, with reduction of the number and the intensity of leprosy reactions. Conclusion: These results suggest that BCG-id induces activation of the initial phase of immunocellular activity: innate human immunity (increase in TNF-α, IL-12 and macrophage activation). Therefore, we conclude that the use of BCG-id could be indicated as an adjuvant to multidrug therapy in treatment of leprosy patients.Keywords: leprosy, immunology, BCG
format article
author Zenha EM
Wambier CG
Novelino AL
Andrade TA
Ferreira MA
Frade MA
Foss NT
author_facet Zenha EM
Wambier CG
Novelino AL
Andrade TA
Ferreira MA
Frade MA
Foss NT
author_sort Zenha EM
title Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study
title_short Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study
title_full Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study
title_fullStr Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study
title_full_unstemmed Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study
title_sort clinical and immunological evaluation after bcg-id vaccine in leprosy patients in a 5-year follow-up study
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/d4fc7c5415494bb586c64eb0b54fbecd
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