Abstract
Summary
Acclimatized rabbits were injected intravenously with 10 ml/kg plasma aliquots from patients febrile with Rocky Mountain spotted fever (104–105°F). Prior to assay, the febrile phase human plasma was processed by repeated absorptions with packed washed rabbit erythrocytes at 4° to remove all detectable heterophile agglutinins. The latter were found in all human plasma samples tested and accounted for their febrile and lethal activity in the rabbit. Ten of 11 absorbed febrile phase human plasma aliquots failed to evoke any febrile response. These negative findings could not be attributed to depression of rabbit thermoregulatory mechanisms or to absorption of human endogenous pyrogen during heterophile agglutinin removal. Since the negative findings might be related to relative insensitivity of the rabbit to human endogenous pyrogen, additional attempts to demonstrate circulating human endogenous pyrogen were performed with human recipients. Five hundred milliliters whole heparinized blood drawn from each of 2 volunteers 30 min before their peak febrile response to S. typhosa endotoxin failed, when reinfused the following morning, to induce an early febrile reaction compatible with an endogenous pyrogen response. Rather, a delayed rise in rectal temperature occurred compatible with residual circulating bacterial endotoxin. A third recipient was given 750 ml of pooled heparinized plasma drawn from 4 other volunteers 1 hr before their peak febrile reaction to S. typhosa endotoxin. Both an early and a delayed febrile response now ensued, compatible with responses to endogenous pyrogen and residual circulating endotoxin, respectively. Reasons for relating the early febrile response to circulating endogenous pyrogen are considered.
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