FEVER PRODUCED BY THE FUNGUS T-BEIGELII INFUSED INTO THE ANTERIOR HYPOTHALAMIC PREOPTIC AREA OF THE RAT

Previously it was reported that a control saline solution infused into the anterior hypothalamic, preoptic area (AH/POA) can induce an inten se fever from an unknown source. To avoid such fevers, cerebral dialys is has been proposed as an alternative procedure, although in nearly a ll experiments on the febrile response, a nonpyrogenic solution is inj ected, not dialyzed, directly into the AH/POA. The purpose of this stu dy was to determine the: a) possible conditions whereby a control solu tion can cause an experimental fever, b) putative organisms which may comprise the source of a centrally induced fever, and c) procedures wh ereby such fevers can be avoided. In twelve adult male Sprague-Dawley rats, an intracerebral cannula for microinjections and a Minimitter te mperature transmitter were implanted within the AH/POA and intraperito neal cavity, respectively. Following recovery, the thermoreactivity of each site in the AH/POA was verified by a microinjection of norepinep hrine which typically lowers body temperature (T(b)) by 0.5-1.0-degree s-C. Two artificial cerebrospinal fluid (CSF) test solutions were used : one exposed to the ambient conditions of the laboratory, and a secon d prepared under pathogen-free conditions, including filtration, to ex clude biological contaminants. A rise in temperature of 0.8-1.0-degree s-C within 1.0 h after microinjection, which increased to as high as 3 .5-degrees-C within 4 h, typically was produced by the contaminated ar tificial CSF solution. The filtered CSF did not evoke a consistent or reliable rise in T(b) of the rats. Microbiological analysis of the fev er-producing CSF revealed its contamination with the fungus, Trichospo ron beigelii. When a suspension of CSF cultured with T beigelii in a c oncentration of almost-equal-to 2.8 x 10(5) colony forming units per m l 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 pyrogenthermosensitive n eurons of the diencephalon may cause an experimental fever. It is envi saged that a clinical fever of unknown origin may be due to the seques tration of a pathogenic mycoplasmic organism within the diencephalon o f the patient. Further, microdialysis is not a necessary procedure for the direct delivery of a substance to the brain. Rather, it is essent ial that the vehicle solution and all components of the microinjection system are free of T. beigelii or other fungal contamination in studi es of the AH/POA in thermoregulation.