Bimodal effect of platelet-activating factor (PAF) on airways responsiveness in the rabbit

The role of platelet-activating factor (PAF) to increase airways responsiveness is unclear. Since PAF has unusual dose-response characteristics in vitro, this study investigated the effects of different doses or concentrations of PAF given by intravenous and aerosol administration in anesthetized rabbits. Aerosol PAF caused a dose-dependent decrease in SGL. Intravenous administration of PAF was associated with thrombocytopenia and neutropenia, whereas aerosol administration of PAF did not alter the numbers of circulatory cells. With either administration, no inflammatory cells were recovered by lavage nor was there evidence of a gross inflammatory process within the lung. Furthermore, there was no evidence of a late asthmatic response. Intravenous PAF caused a bimodal change in airways responsiveness with a significant increase in the effective concentration causing 50% of the maximal change in SGL (EC50SGL) at low doses (0.06-06 micrograms/kg h-1) and a significant decrease in EC50SGL (an increase in responsiveness) at higher doses (1.2-2.4 micrograms/kg/h-1). Aerosol PAF decreased EC50SGL significantly at the higher doses (100-250 micrograms). These changes in EC50SGL, after both administrations, were still apparent at 3 1/2 and 4 h. In conclusion PAF has a dose-dependent, biphasic, and persistent effect on airways responsiveness, which may be independent of circulating inflammatory cells.