FEVER FROM PATHOGENIC FUNGI *

Abstract

The mechanism of fever in fungus infections was studied by systematically examining pathogenic fungi for their capacity to induce fever in rabbits. Intravenous injections of viable Candida albicans, Blastomyces dermatitidis, Histoplasma capsulatum, and Sporotrichum schenckii produced fever, but cultures of Cryptococcus neoformans did not. The fever from these live cultures tooft 2 forms, depending upon the dose and the species of fungus (1) An immediate fever resembling that produced by gram-negative bacterial lipopolysaccharides. This fever began 1 to 3 hrs. after injection, lasted 7 to 8 hrs., and sometimes produced biphasic curves with fever peaks of 1.5 to 4[degree]F at 1 and 3 hrs. (2) A delayed fever, beginning as late as 24 hrs. after inoculation and persisting until death or recovery from infection. The first type of fever curve was attributed to a heat-stable filterable fungus pyrogen, since the fever curve could be reproduced with autoclaved fungus cells or Seitz filtrates of fungus cultures. Unlike gram-negative bacterial pyrogens the fungus pyrogens did not cause tolerance to fever upon repeated daily injections and single massive doses did not produce a shock-like state. Instead, one or more injections of the fungus pyrogen led to increased susceptibility to its toxic effects that produced death from hemorrhagic pneumonia. Aside from pyrogenicity, the main similarity between fungus pyrogens and the pyrogens of gram-negatives, was the marked instantaneous neutropenia and subsequent neutrophilia that followed intravenous injection. The 2nd type of fever curve (i.e., the delayed persistent type) was believed to be a consequence of infection of the tissues. It was observed with experimental candidiasis and sporotrichosis and was not accompanied by positive blood cultures of the infecting fungus. For this reason, and because a circulating pyrogen was found on the 2nd day of infection, it is believed that either the fungus pyrogen or an endogenous tissue pyrogen is released from the infected tissues.