A feverlike response inhibits expression of delayed-type hypersensitivity in rats

To determine the effect of fever on cell-mediated immunity, the preoptic area of male rats was cooled after either a sensitizing or a challenge injection of keyhole-limpet hemocyanin, and the delayed-type hypersensitivity inflammatory response was measured. Cooling the preoptic area for 5 days, starting shortly after the sensitizing injection of antigen, did not speed up the development of the capacity to respond to a challenge injection of antigen nor did it influence the magnitude of the resulting inflammatory response. In sensitized animals, however, cooling the preoptic area for 24 h, starting shortly after the challenge injection of antigen, raised core temperature to an average of 40 degrees C and decreased the magnitude of the inflammatory response by 25%, whereas heating the preoptic area caused a fall in core temperature to an average of 35 degrees C and increased the response by about 25%. There was, in fact, a moderate negative correlation (r = 0.85) between core temperature and the size of the inflammation. Furthermore, the inhibitory effect of cooling the preoptic area could be blocked neither by adrenalectomy nor by diazepam (0.5 mg/kg body wt), a drug that suppresses most endocrine responses to stress. It is therefore suggested that the expression of delayed-type hypersensitivity is inhibited at elevated body temperatures and that fever may thus weaken the defenses of the host against infection.