Blockade of endogenous leukotrienes exacerbates pulmonary histoplasmosis

Autor(es)

Medeiros, Alexandra I. ; Sá-Nunes, Anderson ; Soares, Edson G. ; Peres, Camila M. ; Silva, Célio L. ; Faccioli, Lúcia H. ^[6]

• Tipo de documento: Artigo Científico
• Fonte: Infection and Immunity; v. 72, n. 3, p. 1637-1644, Mar. 2004.
• Área do conhecimento: Ciências Biológicas - Imunologia
• Assunto(s): Ácidos araquidônicos Leucotrienos Infecções bacterianas e micoses Histoplasmose

Resumo

Leukotrienes are classical mediators of inflammatory response. New aspects of leukotriene function have recently been described. We examine here the previously unreported role that leukotrienes play in the regulation of cytokines in a murine model of histoplasmosis. We demonstrate that administration of MK 886, a leukotriene synthesis inhibitor, caused Histoplasma capsulatum-infected mice to die by the day 15 of infection, whereas the correlating death rate in untreated infected mice was 0%. Treating infected animals with MK 886 inhibited leukotriene synthesis but increased leukocyte recruitment to the lungs. Subsequent to this phenomenon, levels of tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and KC chemoattractant cytokines and fungi in the lung parenchyma increased, as did inflammatory response. In contrast, IL-2, IL-5, IL-12, and gamma interferon cytokine levels actually decreased. Thus, murine response to pulmonary histoplasmosis may be leukotriene modulated. This finding may enable us to alter the course of the immune response and inflammation caused by histoplasmosis. The data from the present study suggest an important new strategy for immunologic or drug intervention in human patients. (AU)

• Processo FAPESP: 98/16082-4 - Estudo dos mediadores inflamatórios e moléculas de adesão nas rações inflamatórias aguda e crônica da histoplasmose pulmonar
• Beneficiário: Alexandra Ivo de Medeiros
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 95/09691-6 - Mecanismos envolvidos no recrutamento de eosinófilos e sua participação no desenvolvimento da hiper-reatividade brônquica
• Beneficiário: Lúcia Helena Faccioli
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores