Stimulation of β-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice

György Haskó, Csaba Szabó, Zoltán H. Németh, Andrew L. Salzman, E. Sylvester Vizi

    Research output: Contribution to journalArticle

    83 Scopus citations

    Abstract

    Stimulation of β-adrenoceptors has been shown to regulate the production of various inflammatory mediators. In the present study, we investigated in mice whether ligation of β-adrenoceptors, modulates lipopolysaccharide (LPS)-induced plasma levels of interleukin (IL)-12, interferon-γ (IFN-γ), and IL-10. In BALB/c mice, isoproterenol (1-10 mg kg-1, i.p.), a selective agonist of β-adrenoceptors and also dexamethasone (10 mg kg-1, i.p.) pretreatment 30 min before the administration of LPS suppressed plasma IL-12 (p40 and p70) concentrations as determined at various time points after the LPS challenge. The inhibition of IL-12 release by isoproterenol was prevented by the β-adrenoceptor antagonist propranolol confirming the involvement of β-adrenoceptors in the effect of isoproterenol. Furthermore, pretreatment of the animals with propranolol alone enhanced LPS-induced plasma IL-12, suggesting that endogenous catecholamines inhibit IL-12 production via the β-adrenoceptors. In IL-10 deficient C57BL/6 IL-10(-/-) mice, plasma levels of IL-12 and IFN-γ were significantly higher than in their counterparts, with more than 70-fold increase in IL-12. Furthermore, while augmenting the IL-10 response in C57BL/6 IL-10(+/+), isoproterenol inhibited the production of IL-12 in both the C57BL/6 IL-10(+/+) and C57BL/6 IL-10(-/-) mice, suggesting that the inhibition of IL-12 production by this compound is independent of the increased release of IL-10. Our results demonstrate, for the first time, that stimulation of β-adrenoceptors by isoproterenol or endogenous catecholamines suppresses IL-12 production in vivo.

    Original languageEnglish (US)
    Pages (from-to)57-61
    Number of pages5
    JournalJournal of Neuroimmunology
    Volume88
    Issue number1-2
    DOIs
    StatePublished - Aug 1 1998

    Keywords

    • Cytokines
    • Dexamethasone
    • Lipopolysaccharide
    • Murine
    • β-adrenoreceptors

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Neurology
    • Clinical Neurology

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