FEVER OF UNKNOWN ORIGIN - DUE TO CANDIDA-ALBICANS OR OTHER FUNGI ACTING ON THE HYPOTHALAMUS

Recently, it was shown that cerebrospinal fluid (CSF) contaminated wit h the fungus Trichosporon beigelii produces an intense fever when the organism is microinjected directly into the thermosensitive region of the anterior hypothalamic preoptic area (AH/POA). The purpose of this study was to determine if the AH/POA possesses a corresponding sensiti vity to another fungal organism, Candida albicans. In adult male Sprag ue-Dawley rats, an intracerebral cannula was implanted stereotaxically above the AH/POA and a radio transmitter for the continuous recording of body temperature (T-b) was placed in the peritoneal cavity. After recovery, one of two solutions was microinjected in the AH/POA: a pyro gen-free, filtered artificial CSF and a second cultured with C. albica ns in a concentration of similar to 12 x 10(8) organisms/ml. Whereas t he filtered CSF failed to evoke a significant rise in T-b, C. albicans produced a febrile response of 0.8 - 1.5 degrees C in the rats within 1 h after its microinjection into the AH/POA. This fever persisted ty pically for greater than or equal to 12 h but after 24 h T-b returned to the baseline. Histological examination of the cerebral tissue postm ortem revealed focally extensive granulomatous encephalitis with disse minated inflammation throughout the parenchyma of rats given repeated microinjections of C. albicans. Since C. albicans is a highly potent p yrogen acting directly on thermosensitive neurons, it is envisaged tha t a massive accumulation of the organism within the brain could be res ponsible pathologically for the protracted fever ''of unknown origin'' which gives rise to clinical morbidity.