The Ferrier Lecture, 1974 Body temperature and fever : changes in our views during the last decade

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Abstract
In the past, research on body temperature too often nearly became a branch of physics. A model from physics, the thermostat, was taken to explain the thermoregulatory functions of the anterior hypothalamus. A change occurred when simple methods became available for injecting drugs into the cerebral ventricles of unanaesthetized animals, and when intraventricular injections of noradrenaline and 5-hydroxytryptamine were found to affect temperature. These monoamines appear to exert a tonic influence on temperature by being released from monoaminergic neurons ending in the hypothalamus. But they are not the mediators of endotoxin fever. Nor are they essential for maintaining normal temperature. The mediators of endotoxin fever are E prostaglandins. They raise temperature when injected intraventricularly, appear during endotoxin and lipid A fever in cerebrospinal fluid, but disappear from it when fever is brought down by antipyretics which inhibit prostaglandin synthesis. Many bodily functions, other than temperature, are kept constant. It is the ‘milieu intérieur’ of Claude Bernard that is kept constant. A factor which apparently governs the ‘milieu intérieur’ in the hypothalamus is the calcium ion concentration, since lack of calcium in the hypothalamus raises (and excess lowers) temperature.