Cyclic AMP enhancing drugs modulate eicosanoid release from human alveolar macrophages

Abstract

The effect of the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), salbutamol and sodium nitroprusside was evaluated regarding PGE 2 and LTB 4 release and cAMP and cGMP level in human alveolar macrophages obtained from controls and COPD patients. Basal levels per five million control-respectively COPD alveolar macrophages: cAMP 1.2 and 1.0 pmole; cGMP 8.4 and 9.1 fmole; PGE 2 120 and 63 pg and LTB 4 19.2 and 14.8 pg. In both populations IBMX increased cAMP level by 55–93% and salbutamol+IBMX by 285-252%. Except for the 61% rise in LTB 4 release by salbutamol+IBMX the drugs hardly affected PGE 2 and LTB 4 release from control macrophages. In COPD alveolar macrophages, however, IBMX and IBMX+salbutamol largely reduced PGE 2 release (63 vs 11 pg per 10 6 cells) but less efficiently increased LTB 4. In both macrophage populations sodium nitroprusside (SNP) substantially increased (3–4 fold) cGMP level but did not affect eicosanoid production. Present results indicate that drugs which enhance cAMP level decrease PGE 2 release from COPD macrophages and stimulate the release of LTB 4 a chemotactic mediator involved in bronchial inflammatory reactions.