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2030-01-01
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- INI - Artigos de Periódicos [3025]
- IOC - Artigos de Periódicos [12114]
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THERAPEUTIC FAILURE IN AMERICAN CUTANEOUS LEISHMANIASIS IS ASSOCIATED WITH GELATINASE ACTIVITY AND CYTOKINE EXPRESSION
Leishmaniose tegumentar americana
Metaloproteinases da Matriz
Imunologia da Leishmaniose
Falha terapêutica
Cytokines
American tegumentary leishmaniasis
Matrix metalloproteinases
Therapeutic failure
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil / Divisions of Dermatology and Adult Infectious Disease. Department of Medicine. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Torrance, CA, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Divisions of Dermatology and Adult Infectious Disease. Department of Medicine. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Torrance, CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Divisions of Dermatology and Adult Infectious Disease. Department of Medicine. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Torrance, CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.
Abstract
Cutaneous lesions caused by Leishmania braziliensis infection occasionally heal spontaneously, but with antimonials therapy heal rapidly in approximately 3 weeks. However, about 15% of the cases require several courses of therapy. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that have been implicated in other chronic cutaneous diseases and skin re-epithelialization. These enzymes are controlled by their natural inhibitors [tissue inhibitors of metalloproteinase (TIMPs)] and by some cytokines. Uncontrolled gelatinase activity may result in intense tissue degradation and, consequently, poorly healing wounds. The present study correlates gelatinase activity to therapeutic failure of cutaneous leishmaniasis (CL) lesions. Our results demonstrate an association between gelatinase activity and increased numbers of cells making interferon (IFN)-γ, interleukin (IL)-10 and transforming growth factor (TGF)-β in lesions from poor responders. Conversely, high levels of MMP-2 mRNA and enhanced MMP-2 : TIMP-2 ratios were associated with a satisfactory response to antimonials treatment. Additionally, high gelatinolytic activity was found in the wound beds, necrotic areas in the dermis and within some granulomatous infiltrates. These results indicate the importance of gelatinase activity in the skin lesions caused by CL. Thus, we hypothesize that the immune response profile may be responsible for the gelatinase activity pattern and may ultimately influence the persistence or cure of CL lesions.
Keywords in Portuguese
CitocinasLeishmaniose tegumentar americana
Metaloproteinases da Matriz
Imunologia da Leishmaniose
Falha terapêutica
Keywords
Leishmaniasis immunologyCytokines
American tegumentary leishmaniasis
Matrix metalloproteinases
Therapeutic failure
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