CHRONIC EFFECTS OF INTERLEUKIN-1-BETA ON FEVER, OXYGEN-CONSUMPTION AND FOOD-INTAKE IN THE RAT

Chronic subcutaneous infusion (from osmotic minipumps) of IL-1beta (1 mug/d) in male rats over seven days caused transient (1-3 d) increases in body temperature and reductions in body weight gain and food intake. By day 3, when colonic temperature was similar for vehicle and IL-1 infused groups, the acute responses (increases in temperature and VO2) to a maximal dose (1 mug, sc) of IL-1beta was almost identical in all animals. In a separate study intraperitoneal infusion of the same dose of IL-1beta (1 mug/d) increased the duration of changes in body temperature, weight and food intake, compared to subcutaneous infusion. In further groups of rats, pyrogenic responses to daily injections of IL-1beta (1 mug ip) were sustained for the entire 7 d period, but this treatment did not affect body weight. These data demonstrate that tolerance to infusion of IL-1 is not accompanied by reduced maximal responses to acute administration of IL-1, and indicate that more sustained effects of IL-1 are achieved by intraperitoneal rather than subcutaneous infusions, or by repetitive daily injections of the cytokine. These observations indicate that low levels of IL-1 release, maintained over periods of several days could be responsible for changes in body temperature and energy balance during chronic infections or inflammation.