The mode of action of
cortisone as an
antipyretic has been studied in rabbits challenged with
intravenous injections of bacterial
pyrogens. The
fever induced by
pyromen or
dextran was found to be markedly suppressed when
cortisone was administered in liberal amounts (25 mg. twice daily) for 3 days prior to the challenge. Although the
cortisone effectively blocked the febrile response to both
pyrogens, it failed to influence the transient but marked leucopenia which characteristically precedes the onset of
fever. The
antipyretic action of the
drug also was shown to bear no relation to the activity of the serum factor recently demonstrated by Farr, Grant, and others to be involved in the production of
pyrogen-induced
fever. In preliminary experiments with
typhoid vaccine as the inciting
pyrogen, the presence of serum factor activity in normal blood and its absence in the blood of
pyrogen-tolerant rabbits was confirmed. Subsequently the blood of rabbits treated with antipyretically effective doses of
cortisone was shown to contain just as much serum factor activity as that of normal rabbits. In addition, previous incubation of the
pyrogen with serum factor failed to influence the
antipyretic effect of the
drug. It is concluded from these findings that in suppressing
pyrogen fever,
cortisone acts neither upon the leucopenic reaction nor upon the
fever-accelerating factor of the serum. By exclusion it would appear that the
drug must influence some later stage of the
fever-producing process. The mechanisms involved in the later stages of the response to exogenous
pyrogen remain undefined, and the need for determining whether they are related to the prefebrile leucopenia is emphasized.