Body temperature modulates the effect of platelet-activating factor (PAF) on airways responsiveness in the rabbit

Abstract

Platelet-activating factor (PAF) is a potent mediator known to cause bronchoconstriction and increase airways responsiveness. In vitro studies have shown that the effects of PAF on cell function can be very temperature-dependent. The aim of the current study was to investigate the effect of elevated body temperature on numbers of circulating cells and pulmonary function in anesthetized rabbits in response to PAF. PAF was given intravenously, at a dose of 1.2 micrograms/kg hour, whereas the control experiments were performed after the animals received a saline infusion. Alteration of airways function was assessed by measuring specific pulmonary conductance (SGL) and dose-response relationships to inhaled histamine, where airways responsiveness was expressed as the effective concentration causing 50% of maximal change in specific airways conductance (EC50SGL). The rabbits were studied at two body temperatures: a normal temperature (rectal temperature of 39.8 C), and a higher temperature (rectal temperature 41.2 degrees C). Changes in circulating inflammatory cells, plasma corticosterone concentrations and in hematocrit were also monitored, to examine some potential mechanisms which might explain why body temperature altered airways responsiveness. At the normal body temperature infusion of PAF caused a significant increase in airways responsiveness (p less than 0.025), while at the high body temperature, there was a significant decrease in responsiveness (p less than 0.025). However, at both body temperatures, a profound but similar thrombocytopenia and neutropenia was observed. While plasma corticosterone levels and hematocrit showed increases coincident with the infusion of PAF, this response was unchanged by altering body temperature. We conclude that increased body temperature reduces the effect of PAF on airways responsiveness apparently through a mechanism independent of PAF effects on hemoconcentration, plasma corticosterone or circulating inflammatory cells.