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The taming of IL‐12: suppressing the production of proinflammatory cytokines
Author(s) -
Sutterwala Fayyaz S.,
Mosser David M.
Publication year - 1999
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 - 10.1002/jlb.65.5.543
Subject(s) - proinflammatory cytokine , biology , production (economics) , immunology , interleukin , microbiology and biotechnology , cytokine , inflammation , economics , macroeconomics
Interleukin (IL)‐12 is a cytokine that possesses both proinflammatory and immunoregulatory activity. IL‐12, and the interferon‐γ (IFN‐γ) that is induced by IL‐12, play central roles in the development of the Th1‐type immune responses that are required for immunity to intracellular pathogens. Recently a number of these pathogens, including Leishmania, measles virus, and human immunodeficiency virus (HIV), have been shown to subvert the development of cell‐mediated immunity by actively inhibiting the production of IL‐12. Similarly, the ligation of phagocytic receptors on macrophages has also been shown to suppress IL‐12 production. The suppression of IL‐12 production by receptor ligation occurs by at least two distinct mechanisms: one involves a direct inhibition of gene transcription and the other depends on the production of inhibitory cytokines. We review studies in which IL‐12 has been experimentally manipulated, and we compare the mechanisms by which this regulation can occur. Because the IL‐12 that is produced during acute inflammation and chronic autoimmune disorders can lead to exacerbated disease, the development of pharmacological means to suppress IL‐12 production is currently under investigation. This review focuses on the production of IL‐12 by antigen‐presenting cells and the methods by which the down‐regulation of IL‐12 production can be exploited either by pathogens or for therapeutic ends. J. Leukoc. Biol. 65: 543–551; 1999.