SYNERGISM BETWEEN IL-1-BETA AND TNF-ALPHA ON THE ACTIVITY OF THE PITUITARY-ADRENAL AXIS AND ON FOOD-INTAKE OF RATS

We investigated the effects of separate and combined intraperitoneal a dministration for 3 days of recombinant human interleukin-1 beta (IL-1 ) and recombinant human tumor necrosis factor-alpha (TNF) on plasma ad renocorticotropic hormone (ACTH) and corticosterone (B) levels, adrena l weight, food intake, and rectal temperature. Rats were equipped with a jugular cannula for daily blood sampling and with an intraperitonea lly implanted Alzet osmotic minipump loaded with either saline, IL-1 ( 2.0 mu g/day), TNF (0.2, 2.0, or 10.0 mu g/day), or IL-1 in combinatio n with TNF. Plasma ACTH and B levels and adrenal weight were significa ntly increased, in a dose-dependent way, by simultaneous infusion of I L-1 and TNF but not by administration of either cytokine alone. Chroni c administration of IL-1 alone induced a significant decrease in food intake and a significant elevation of rectal temperature, whereas infu sion of only the highest dose of TNF significantly elevated rectal tem perature. Coinfusion of IL-1 and TNF induced both effects in a dose-de pendent and synergistic way. Our data show that simultaneous infusion of IL-1 and TNF in rats has a synergistic effect on the activity of th e pituitary-adrenal axis as well as on food intake and rectal temperat ure. The existence of two pathways, which act synergistically, may inc rease the sensitivity of the host to respond to subtle inflammatory st imuli.