Peripheral endocrine and metabolic responses to centrally administered interleukin-1

It is becoming increasingly apparent that interleukin-1 (IL-1) acts systemically and centrally to play an important role in regulating the hormonal and metabolic response to stress, infection, and trauma. The aim of this study was to observe the peripheral metabolic and endocrine responses to 15, 25, and 50 ng intracerebroventricular (i.c.v.) recombinant IL-1 beta in awake, freely moving rats over a 6-hour period. The rate and duration of elevation of temperature and plasma corticosterone and glucose were dose-dependent and did not return to control levels until 6 or more hours later. Hepatic glycogen content 6 h after i.c.v. IL-1 was 58, 52 and 78% of control after 15, 25, and 50 ng, respectively. The plasma insulin response to elevated plasma glucose in rats treated with 15 ng was absent in those treated with 25 and 50 ng. Responses of plasma glucagon to each dose of IL-1 were not significantly different from control responses. PEPCK enzyme activity was diminished to 60, 66, and 81% of control after 15, 25, and 50 ng IL-1, respectively. No changes of body temperature or plasma corticosterone were observed when 25 or 50 ng IL-1 were injected intravenously. These results are strong evidence that central actions of IL-1 significantly affect peripheral glycemia via classical hepatic and endocrine adjustments.