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Role of IL‐12 in macrophage activation during intracellular infection: IL‐12 and mycobacteria synergistically release TNF‐α and nitric oxide from macrophages via IFN‐γ induction
Author(s) -
Xing Zhou,
Zganiacz Anna,
Santosuosso Micheal
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.6.897
Subject(s) - macrophage , intracellular , biology , macrophage activating factor , nitric oxide , cytokine , tumor necrosis factor alpha , microbiology and biotechnology , interferon gamma , in vitro , immunology , macrophage inflammatory protein , alveolar macrophage , interleukin , biochemistry , endocrinology
IL‐12 is believed to play an important role in cell‐mediated immunity against intracellular infection primarily by acting on T and NK cells. Recent evidence has suggested, however, that IL‐12 has broader cellular targets than previously thought. In this study, we examined the role of IL‐12 in macrophage TNF‐α and nitric oxide (NO) release by using an in vitro model of intracellular infection. IL‐12 alone released relatively little TNF‐α and NO, whereas live mycobacteria alone released TNF‐α markedly but little NO from murine alveolar macrophages. However, IL‐12 and mycobacteria together enhanced TNF‐α and NO release synergistically. Because IL‐12 and mycobacteria also released IFN‐γ from macrophages synergistically, and exogenous IFN‐γ with mycobacteria enhanced TNF‐α and NO release synergistically, we examined the role of endogenous IFN‐γ in IL‐12/mycobacteria‐stimulated macrophage activation. Using macrophages from mice deficient in IFN‐γ, we found that IL‐12/mycobacteria‐enhanced macrophage TNF‐α and NO release was mediated through endogenous IFN‐γ. We further demonstrated that IFN‐γ and mycobacteria together had a selective effect on macrophage cytokine release because they released TNF‐α synergistically but not macrophage chemotactic protein‐1 (MCP‐1). These findings reveal that IL‐12 can activate macrophages potently during intracellular infection, and this activating effect is mediated primarily through its effect on macrophage IFN‐γ release.