Role of the Posterior Hypothalamus in Mediating the Lethal Action of Bacterial Endotoxin in the Rat

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Abstract
Summary: The LD50 of endotoxin is approximately twice as great when given intracardially as when given into the carotid artery. Elevation of ambient temperature increases the body temperature of rats and decreases the LD50 strikingly. Rats maintained at elevated temperatures respond to endotoxin with hyperthermia rather than the usual hypothermia. In hyperthermic animals, the intracarotid route is still about twice as lethal as the intracardiac. Stereotactic ablation experiments, performed to localize the site of unusual sensitivity to endotoxin in the brain, indicated that lesions in the paraolfactory area, superior colliculus or lateral hypothalamus had no effect on the lethal action of endotoxin. However, lesions in the posterior hypothalamus protected rats against an otherwise lethal dose of endotoxin, and did so in the absence of significant alterations in body temperature. Lesions in the anterior hypothalamus produced hyperthermia and were associated with decreased resistance to the lethal action of endotoxin. It is concluded that there are graded sites of sensitivity to endotoxin, and that the posterior hypothalamic area is the most sensitive so far discerned. The lethal action of endotoxin is therefore manifested, in part at least, through the mediation of the posterior hypothalmus. No conclusions are drawn as to whether the action of endotoxin is direct or indirect, or related to hypersensitivity.