Control of experimental pulmonary tuberculosis depends more on immunostimulatory leukotrienes than on the absence of immunosuppressive prostaglandins

Autor(es)

Peres-Buzalaf, C. ^[1] ; de Paula, L. ^[1] ; Frantz, F. G. ^[1] ; Soares, E. M. ^[1] ; Medeiros, A. I. ^[1] ; Peters-Golden, M. ^[2] ; Silva, C. L. ^[3] ; Faccioli, L. H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Sao Paulo - Brazil

^[2] Univ Michigan Hlth Syst, Div Pulm & Crit Care Med, Dept Internal Med, Ann Arbor, MI - USA

^[3] Univ Sao Paulo, Dept Bioquim & Imunol, Fac Med Ribeirao Preto, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS; v. 85, n. 2, p. 75-81, AUG 2011.
• Citações Web of Science: 18

Resumo

Prostaglandins (PGs) and leukotrienes (LTs) are produced in Mycobacterium tuberculosis (Mtb)-infected lungs and have immune suppressive and protective effects, respectively. Considering that both of these mediators are produced during mycobacterial infection, we investigated the specific and relative biological importance of each in regulating host response in experimental tuberculosis. Administration of celecoxib, which was found to reduce lung levels of PGE(2) and increase LTB(4), enhanced the 60-day survival of Mtb-infected mice in 14%. However administration of MK-886, which reduced levels of LTB(4) but did not enhance PGE(2), reduced 60-day survival from 86% to 43% in Mtb-infected mice, and increased lung bacterial burden. MK-886 plus celecoxib reduced survival to a lesser extent than MK-886 alone. MK-886- and MK-886 plus celecoxib-treated animals exhibited reduced levels of the protective interleukin-12 and gamma-interferon. Our findings indicate that in this model, the protective effect of LTs dominates over the suppressive effect of PGs. (C) 2011 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 00/09663-2 - Estudos de novas vacinas e terapia gênica contra tuberculose
• Beneficiário: Celio Lopes Silva
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 01/12400-6 - Participacao de prostaglandinas e leucotrienos na fase aguda da tuberculose experimental.
• Beneficiário: Camila Peres Buzalaf
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 02/12856-2 - Modulação das respostas imunes inata e adquirida por leucotrienos e prostaglandinas
• Beneficiário: Lúcia Helena Faccioli
• Linha de fomento: Auxílio à Pesquisa - Temático