Central adaptation to chronic administration of interleukin-1beta (IL-1beta) in rats

Interleukin-1beta (IL-1beta), a cytokine, has been shown to induce a number of central and neuroendocrine effects. Prolonged treatment with IL-1beta is associated with adaptive responses in feeding, body temperature and hormone profiles. The purpose of the present study was to see if these effects are accompanied by changes in hypothalamic norepinephrine (NE) and to compare it with the acute effects of IL-1beta. Adult male Sprague-Dawley rats were treated (i.p.) with 5 microg of IL-1beta once (acute) or daily for 5 consequent days (chronic). The control animals received an injection of the vehicle for IL-1beta (0.1% PBS-BSA). Body weight, food intake, and rectal temperature were monitored daily. At the end of treatment, the animals were sacrificed, and specific areas of the hypothalamus were microdissected and analyzed for NE concentrations. Corticosterone levels were measured in the serum. Both acute and chronic IL-1beta treatment produced significant changes in a number of parameters. However, there were marked differences between the two treatment regimens. While acute treatment with IL-1beta increased NE concentrations in both the paraventricular nucleus and the median eminence (ME), chronic treatment increased NE concentrations only in the ME. A corresponding increase in serum corticosterone levels was observed with acute IL treatment. Chronic treatment with IL-1beta decreased body weight, and produced an initial decrease in food intake which returned to control levels by the fourth day of treatment. Chronic IL treatment also produced an initial increase in body temperature that returned to control levels by day 4. These results indicate that the effects of IL-1beta on central and neuroendocrine functions are dependent on the duration of the treatment and that the adaptive responses observed in feeding and body temperature after chronic IL treatment are accompanied by similar responses in brain NE.