Interactions between local inflammatory and systemic haematological effects of PAF-acether in the rat.

Intraplantar injections of PAF-acether into the rat paw (0.025-16 micrograms/paw) were followed by a bell-shaped dose-response curve for oedema. In parallel to the ascending phase (0.25-2 micrograms/paw) a significant leukopenia was observed whereas thrombocytopenia, haemoconcentration and leukocytosis were seen during the descending phase (4-16 micrograms/paw) as was also observed after the i.v. injection of PAF-acether. I.v. injections of PAF-acether inhibited dose dependently the oedema induced by PAF-acether itself but were inactive against serotonin. Dexamethasone (0.1 mg/kg) inhibited the PAF-acether-induced thrombocytopenia and haemoconcentration but failed to modify the leukocytosis whereas aspirin (100 mg/kg) and indomethacin (1.0 mg/kg) inhibited only the haemoconcentration. The PAF-acether antagonist 48740 RP blocked the systemic haematological alterations and restored the auto-reduced oedema induced by a high dose of PAF-acether (16 micrograms/paw) but was unable to inhibit the paw oedema induced by PAF-acether. It is suggested that haemoconcentration, thrombocytopenia and leukocytosis are independent phenomena associated with the presence of PAF-acether in the bloodstream, these haematological changes and the local oedema induced by PAF-acether involve distinct mechanisms and the auto-inhibitory property of PAF-acether is not restricted to in vitro situations, but extends to local inflammation.