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

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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
Pages (from-to)468-472
Number of pages5
JournalEuropean journal of immunology
Volume28
Issue number2
DOIs
Publication statusPublished - Feb 1 1998

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Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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