INFLUENCE OF A PENTOXIFYLLINE-ANALOG ON THE GRANULOCYTE-MEDIATED PULMONARY MEDIATOR RELEASE AND VASCULAR REACTION

The influence of a novel pentoxifylline-analogue, HWA 138, on the poly morphonuclear neutrophil leukocYte (PMN)-mediated changes in pulmonary resistance and mediator release was investigated in the isolated perf used and ventilated rabbit lung model. Isolated, washed human granuloc ytes were injected into the pulmonary artery and stimulated by either 10(-6) mol/L N-formyl-L-leucin-methionyl-L-phenylalanin (FMP) or 3 x 1 0(-8) mol/L phorbol 12-myristate 13-acetate (PMA) in the presence or a bsence (controls) of HWA 138 (10(-4) mol/L). Shortly after granulocyte activation, there was a massive generation and release of thromboxane (>110 pg/ml) and histamine (150-400 nmol/L), with an acute increase o f pulmonary artery pressure (>8 mmHg) in the control groups. Applicati on of HWA 138 almost completely suppressed mediator formation and rele ase as well as pulmonary vascular reaction in the FMP stimulated group . In contrast to this, HWA 138 was unable to influence either mediator release, the pulmonary pressure reaction or interstitial edema format ion following PMA stimulation. In the present model, HWA 138 is suppos ed to be effective via granulocytes by decreasing mediator release, ob viously due to burst reaction.