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

Abstract

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.

• Authors: C Peres-Buzalaf, L de Paula, F G Frantz, E M Soares, A I Medeiros, M Peters-Golden, C L Silva, L H Faccioli
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 85 Issue 2 Pg. 75-81 (Aug 2011) ISSN: 1532-2823 [Electronic] Scotland
• PMID: 21621991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Immunosuppressive Agents
• Indoles
• Leukotrienes
• Lipoxygenase Inhibitors
• Prostaglandins
• MK-886
• Nitric Oxide

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Bronchoalveolar Lavage Fluid (immunology, microbiology)
• Cytokines (immunology, metabolism)
• Immunosuppressive Agents (pharmacology)
• Indoles (pharmacology)
• Leukotrienes (immunology, pharmacology)
• Lipoxygenase Inhibitors (pharmacology)
• Lung (drug effects, immunology, microbiology)
• Male
• Mice
• Mice, Inbred BALB C
• Mycobacterium tuberculosis (drug effects, growth & development, immunology)
• Nitric Oxide (immunology, metabolism)
• Prostaglandins (immunology, pharmacology)
• Tuberculosis, Pulmonary (immunology, pathology, prevention & control)