Suppression of IL-12 production by phosphodiesterase inhibition in murine endotoxemia is IL-10 independent

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

    Research output: Contribution to journalArticle

    65 Scopus citations

    Abstract

    Phosphodiesterase (PDE) inhibitors are potent regulators of various immune processes. Immune cells contain type IV and type III PDE. Here we studied in mice the effects of rolipram, a selective PDE IV inhibitor, and amrinone, a selective PDE III blocker, on plasma levels of IL-12 (p70), IFN-γ, IL-1, TNF-α, and nitric oxide (NO) induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) (80 mg/kg). Pretreatment of BALB/c mice with both rolipram (1-25 mg/kg) and amrinone (10-100 mg/kg) decreased plasma IL-12 levels in a dose-dependent manner. Similarly, LPS-elicited plasma IFN-γ concentrations were suppressed by both rolipram and amrinone. However, LPS-induced plasma IL-1α levels were not affected by either of these compounds. In addition, rolipram inhibited IL-12, IFN-γ, TNF-α and nitrite/nitrate (breakdown products of NO) production in C57BL/6 IL-10(+/+) mice as well as in their IL-10-deficient counterparts (C57BL/6 IL-10(-/-)). Our results suggest that rolipram and amrinone decrease the immune activation in endotoxemia through inhibition of the production of pro-inflammatory mediators IL-12, IFN-γ, TNF-α and NO. These effects are not the consequences of the increase in IL-10 production by PDE inhibition.

    Original languageEnglish (US)
    Pages (from-to)468-472
    Number of pages5
    JournalEuropean Journal of Immunology
    Volume28
    Issue number2
    DOIs
    StatePublished - Feb 1 1998

    Keywords

    • Cyclic AMP
    • Cytokine
    • IFN-γ
    • Lipopolysaccharide
    • TNF-α

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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