An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-γ production and prevents lethality in endotoxemic mice

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

    Research output: Contribution to journalArticle

    130 Scopus citations

    Abstract

    We have recently observed that the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) augments interleukin-10 and inhibits tumor necrosis factor-α production in endotoxemic mice. In the present study, we extended our investigations into the effect of this compound on the bacterial lipopolysaccharide (endotoxin)-induced inflammatory response in the BALB/c, as well as in the C57BL/6 interleukin-10(+/+) and the interleukin-10 deficient C57BL/6 interleukin-10(0/0) mice strains. In the BALB/c mice, i.p. pre-treatment with IB-MECA (0.2 and 0.5 mg/kg) decreased lipopolysaccharide (60 mg/kg i.p.)-induced plasma levels of interleukin-12 (p40 and p70), interferon-γ, and nitrite/nitrate (breakdown products of nitric oxide (NO)). On the other hand, pre-treatment with this compound failed to influence lipopolysaccharide-induced plasma interleukin-1α, interleukin-6, and corticosterone concentrations. Similar to its effect in BALB/c mice, IB-MECA enhanced the release of interleukin-10 in the C57BL/6 interleukin-10(+/+) mice. Furthermore, IB-MECA inhibited the production of interleukin-12, interferon-γ, and NO in both the C57BL/6 interleukin-10(+/+) and C57BL/6 interleukin-10(0/0) mice, suggesting that the inhibition of pro-inflammatory cytokine production by this compound is independent of the increased release of interleukin-10. Finally, pre-treatment with this compound protected mice against lipopolysaccharide (60 mg/kg i.p.)-induced lethality. These results indicate that stimulation of adenosine A3 receptors has potent anti-inflammatory effects and may represent a potential strategy in the treatment of septic shock and other inflammatory diseases. Copyright (C) 1998 Elsevier Science B.V.

    Original languageEnglish (US)
    Pages (from-to)261-268
    Number of pages8
    JournalEuropean Journal of Pharmacology
    Volume358
    Issue number3
    DOIs
    StatePublished - Oct 9 1998

    Keywords

    • Cytokine
    • Inflammation
    • Inflammatory mediator
    • Lipopolysaccharide
    • Nitric oxide (NO)
    • Shock

    ASJC Scopus subject areas

    • Pharmacology

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