title: Fever of unknown origin: due to C. albicans or other fungi acting on the hypothalamus?
abstract: Recently, it was shown that cerebrospinal fluid (CSF) contaminated with 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 sensitivity to another fungal organism, Candida albicans. In adult male Sprague-Dawley rats, an intracerebral cannula was implanted stereotaxically above the AH/POA and a radio transmitter for the continuous recording of body temperature (Tb) was placed in the peritoneal cavity. After recovery, one of two solutions was microinjected in the AH/POA: a pyrogen-free, filtered artificial CSF and a second cultured with C. albicans in a concentration of approximately 12 x 10(8) organisms/ml. Whereas the filtered CSF failed to evoke a significant rise in Tb, 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 typically for > or = 12 h but after 24 h Tb returned to the baseline. Histological examination of the cerebral tissue postmortem revealed focally extensive granulomatous encephalitis with disseminated inflammation throughout the parenchyma of rats given repeated microinjections of C. albicans. Since C. albicans is a highly potent pyrogen acting directly on thermosensitive neurons, it is envisaged that a massive accumulation of the organism within the brain could be responsible pathologically for the protracted fever "of unknown origin" which gives rise to clinical morbidity.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
authors.forename: V S
authors.initials: VS
authors.lastname: Barwick
authors.forename: M H
authors.initials: MH
authors.lastname: Wooten
authors.forename: J F
authors.initials: JF
authors.lastname: Bradfield
authors.forename: R D
authors.initials: RD
authors.lastname: Myers
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D002176:Candida albicans / Q000502:physiology*; D005335:Fever of Unknown Origin / Q000382:microbiology* / Q000473:pathology; D005658:Fungi / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000382:microbiology* / Q000473:pathology; D008297:Male; D008845:Microinjections; D011301:Preoptic Area / Q000382:microbiology* / Q000473:pathology; D011846:Radio Waves; D051381:Rats; D017207:Rats, Sprague-Dawley