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

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

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 1998
Externally publishedYes

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Rolipram
Endotoxemia
Amrinone
Phosphoric Diester Hydrolases
Interleukin-12
Interleukin-10
Type 3 Cyclic Nucleotide Phosphodiesterases
Type 4 Cyclic Nucleotide Phosphodiesterase
Lipopolysaccharides
Nitric Oxide
Phosphodiesterase Inhibitors
Interleukin-1
Nitrites
Intraperitoneal Injections
Nitrates
Escherichia coli

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Suppression of IL-12 production by phosphodiesterase inhibition in murine endotoxemia is IL-10 independent. / Haskó, György; Szabo, Csaba; Németh, Zoltán H.; Salzman, Andrew L.; Vizi, E. Sylvester.

In: European Journal of Immunology, Vol. 28, No. 2, 02.1998, p. 468-472.

Research output: Contribution to journalArticle

Haskó, György ; Szabo, Csaba ; Németh, Zoltán H. ; Salzman, Andrew L. ; Vizi, E. Sylvester. / Suppression of IL-12 production by phosphodiesterase inhibition in murine endotoxemia is IL-10 independent. In: European Journal of Immunology. 1998 ; Vol. 28, No. 2. pp. 468-472.
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