Studies in cryptococcal fever. I. Responses to intact organisms and to a soluble agent derived from cryptococci.

It is a long-established clinical observation that most microbial infections are associated with fever. With many of these agents, however, the pathogenesis of fever has been only recently elucidated and it is apparent that several different mechanisms may be implicated.' The following studies were undertaken to compare fevers induced in rabbits by a nonpathogenic fungus, Cryptococcus albidus, with those reported in similar models employing viruses' and both Gram-negative' and Gram-positive bacteria."In contrast to extensive investigations with other microbes, there are only a few previous studies demonstrating the pyrogenicity of various fungi." Both the whole cells and soluble products of these microorganisms have been utilized to produce fever, but hitherto no systematic attempt has been made to determine if different pyrogenic mechanisms were involved; nor has there been any previous effort to establish the relationship of fevers induced by fungi to those caused by bacterial pyrogens, the co-called "endotoxins" of Gram-negative bacteria. In the following studies, evidence is presented that both living and dead cells of this cryptococcal species are pyrogenic in normal rabbits, whereas its soluble products seem to cause fever only, or primarily, in specifically sensitized animals. Further, in their pyrogenic actions, the cells and soluble products of this fungus appear to be clearly separable from each other, as well as from Gram-negative bacterial endotoxins, and in this regard resemble fever-inducing factors associated with the cells and culture filtrates, respectively, of certain phage types of staphylococci.1-17