title: 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.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Peres-Buzalaf
authors.forename: L
authors.initials: L
authors.lastname: de Paula
authors.forename: F G
authors.initials: FG
authors.lastname: Frantz
authors.forename: E M
authors.initials: EM
authors.lastname: Soares
authors.forename: A I
authors.initials: AI
authors.lastname: Medeiros
authors.forename: M
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
authors.forename: L H
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D015289:Leukotrienes / Q000276:immunology / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D011453:Prostaglandins / Q000276:immunology / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002722:Chlorobenzenes
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; D007211:Indoles; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D009569:Nitric Oxide; D011453:Prostaglandins; C060893:MK-886; D002722:Chlorobenzenes