INHIBITION BY THE ANTI-MITOTIC DRUG DOXORUBICIN OF PLATELET-ACTIVATING-FACTOR-INDUCED LATE EOSINOPHIL ACCUMULATION IN RATS

Platelet-activating factor (PAF) has been shown, in the rat model of p leural inflammation, to induce the generation of an intermediate prote ic factor able to cause eosinophil proliferation in vitro. This study was undertaken to investigate the effect of the anti-mitotic compound doxorubicin on PAF-induced eosinophilia in rats, in order to evaluate the contribution of local cell proliferation to this phenomenon. The l ate eosinophil infiltration caused by another chemoattractant leukotri ene B-4 was used for comparison. We observed that local treatment with doxorubicin (20 and 40 mu g/cavity), given 6 h after PAF(1 mu g/cavit y), suppressed the eosinophil accumulation within 24 h, whilst only th e higher dose was effective when the drug was given 12 h post-PAF. An effect on chemotaxis was ruled out, since local doxorubicin (40 mu g/c avity) failed to modify the eosinophil migration noted 24 h after leuk otriene B-4 (0.5 mu g/cavity) and the neutrophil/eosinophil infiltrati on noted at 6 h after PAF injection. Transfer of the pleural fluids co llected 6 h after PAF from donors to recipient rats caused significant eosinophil accumulation in the recipient rats, an effect which was in hibited by the co-administration of doxorubicin (40 mu g/cavity). No i nhibitory effect was noted when the drug was given 6 h after the pleur al fluids were transferred. We also found no change in the number of b lood or bone marrow eosinophils after PAF stimulation. We conclude tha t doxorubicin selectively impaired the late eosinophil accumulation tr iggered by PAF in the pleural cavity of rats, clearly indicating that local cell proliferation seems to contribute to the development of thi s inflammatory response. (C) 1998 Elsevier Science B.V. All rights res erved.