Fever produced by the fungus T. beigelii infused into the anterior hypothalamic preoptic area of the rat

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Previously it was reported that a control saline solution infused into the anterior hypothalamic, preoptic area (AH/POA) can induce an intense fever from an unknown source. To avoid such fevers, cerebral dialysis has been proposed as an alternative procedure, although in nearly all experiments on the febrile response, a nonpyrogenic solution is injected, not dialyzed, directly into the AH/POA. The purpose of this study was to determine the: a) possible conditions whereby a control solution can cause an experimental fever; b) putative organisms which may comprise the source of a centrally induced fever; and c) procedures whereby such fevers can be avoided. In twelve adult male Sprague-Dawley rats, an intracerebral cannula for microinjections and a Minimitter temperature transmitter were implanted within the AH/POA and intraperetoneal cavity, respectively. Following recovery, the thermoreactivity of each site in the AH/POA was verified by a microinjection of norepinephrine which typically lowers body temperature (T b) by 0.5–1.0°C. Two artificial cerebrospinal fluid (CSF) test solutions were used: one exposed to the ambient conditions of the laboratory, and a second prepared under pathogen-free conditions, including filtration, to exclude biological contaminants. A rise in temperature of 0.8–1.0°C within 1.0 h after microinjection, which increased to as high as 3.5°C within 4 h, typically was produced by the contaminated artificial CSF solution. The filtered CSF did not evoke a consistent or reliable rise in T b of the rats. Microbiological analysis of the fever-producing CSF revealed its contamination with the fungus, Trichosporon beigelii. When a suspension of CSF cultured with T. beigelii in a concentration of ≈2.8 × 10 5 colony forming units per ml was microinjected to the AH/POA, fever corresponding to that evoked by the T. beigelii-contaminated CSF ensued. These results demonstrate that a fungal organism acting directly on the pyrogen-thermosensitive neurons of the diencephalon may cause an experimental fever. It is envisaged that a clinical fever of unknown origin may be due to the sequestration of a pathogenic mycoplasmic organism within diencephalon of the patient. Further, microdialysis is not a necessary procedure for the direct delivery of a substance to the brain. Rather, it is essential that the vehicle solution and all components of the microinjection system are free of T. beigelii or other fungal contamination in studies of the AH/POA in thermoregulation.