Neurophysiology of fever

Fever is a primary disorder of thermoregulation and a common clinical sign in many diseases. It is characterized by an upward displacement in the level at which body temperature is regulated. Early attempts to study hypothalamic neuronal activity in relation to fever described the behavior of isolated single units after intravenous injections of endotoxin pyrogen. It was concluded that the thermosensitivity of many warm-sensitive units was depressed after pyrogen injections, but due to the indirect technique employed, it is not possible to distinguish whether this observation is the cause or result of fever. A decrease in hypothalamic thermosensitivity is contrary to observations made during fever in conscious animals. More specific applications of pyrogenic stimuli such as prostaglandin E1 onto individual hypothalamic neurons using the technique of microelectrophoresis have not borne out these earlier observations. A major obstacle to studying the neurophysiology of thermoregulation and fever is the absence of any obvious correlation between neuroanatomy and function in the hypothalamus. Present methods of identifying and classifying hypothalamic cells as participants in thermoregulation are patently inadequate. Until a more specific correlation between anatomy and function is established, the neurophysiological mechanisms of fever will remain obscure.