In 1948 Beeson (3) reported that granulocytes contain an endogenous pyrogen, which was later (4,5) shown to differ from the pyrogenic endotoxin of gram negative bacteria. Considerable work on the pathogenesis of fever by several investigators eventually yielded an experimental model for it (Fig. 1).

This paper reports the results of a study by and of chairmen of pathology departments in American and Canadian medical schools directed toward discovering chairmen's perceptions and attitudes about the future of pathology. Over 100 of a total of 143 chairmen participated in some or all phases of this study in which the Delphi approach was used. Sixty-five chairmen completed all four rounds of questionnaires. Most chairmen are deeply concerned about increasing federal regulation of medicine. They expect to play a greater role in all phases of medical education with more emphasis on the basic science aspects of pathology. They also foresee a desirable shifting of residency training programs away from small hospitals to the larger medical centers. This shift will result in fewer but longer training programs.

The metabolic inhibitors, actinomycin D, cycloheximide, puromycin dihydrochloride, puromycin aminonucleoside, and p-fluorophenylalanine did not inhibit the release of leukocytic pyrogen whether endotoxin was preincubated with cells for 20 min at 37 degrees C before addition of inhibitor or inhibitor was preincubated with cells for 1 hr before addition of endotoxin. On the other hand, cortison inhibited release of pyrogen under both experimental conditions. Poly(I): poly(C) was not effective in inducing rabbit leukocytes to produce an endogenous pyrogen.

Summary Estrogen in the form of estradiol benzoate and cortisone as the acetate are shown to have an effect on thermoregulation in the female rabbit. Estrogen causes a significant, consistent depression of basal body temperature and cortisone causes a transient hyperthermia. Conversely, neither of these hormones is capable of significantly influencing the thermoregulatory response of the rabbit to leukocytic pyrogen.

These studies were designed to determine whether the antipyretic action of glucocorticoids is due 1) to inhibition of the formation or release of leukocytic pyrogen (L.P.) or 2) the suppression of the action of L.P. on the central nervous system. The pyrogenic response to endotoxin of adult New Zealand rabbits pretreated for 3 days with glucocorticoid is about 1/4 that of saline controls. The pyrogenic response to L.P. of animals pretreated as above with glucocorticoidglucocorticoid is not significantly different from that of control animals. Rabbit buffy coat cells incubated with endotoxin and glucocorticoid produce significantly less L.P. than cells incubated with endotoxin alone. These studies suggest that glucocorticoids are antipyretic because they act on leukocytes to inhibit the formation and/or release of active leukocytic pyrogen. (Endocrinology82: 195, 1968)

Sodium salicylate is antipyretic in experimental endotoxin fevers in rabbits but is not significantly antipyretic in fevers induced by leucocytic pyrogen. The in vitro production of pyrogen by leucocytes is significantly decreased by salicylate. The accumulated evidence suggests that in rabbits the antipyretic effect of salicylate is not central on the hypothalamus but is peripheral on the leucocyte to inhibit formation or release of its pyrogen.