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

Eur J Immunol. 1998 Feb;28(2):468-72. doi: 10.1002/(SICI)1521-4141(199802)28:02<468::AID-IMMU468>3.0.CO;2-Z.


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-gamma, IL-1, TNF-alpha, 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-gamma concentrations were suppressed by both rolipram and amrinone. However, LPS-induced plasma IL-1alpha levels were not affected by either of these compounds. In addition, rolipram inhibited IL-12, IFN-gamma, TNF-alpha 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-gamma, TNF-alpha and NO. These effects are not the consequences of the increase in IL-10 production by PDE inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Amrinone / administration & dosage
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Endotoxemia / enzymology*
  • Endotoxemia / immunology*
  • Injections, Intraperitoneal
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / deficiency
  • Interleukin-10 / physiology*
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / blood
  • Lipopolysaccharides / administration & dosage
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / antagonists & inhibitors
  • Pyrrolidinones / administration & dosage
  • Rolipram
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Lipopolysaccharides
  • Pyrrolidinones
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Amrinone
  • Rolipram