Chronic effects of interleukin-1 beta on fever, oxygen consumption and food intake in the rat.

Chronic subcutaneous infusion (from osmotic minipumps) of IL-1 beta (1 microgram/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 microgram, sc) of IL-1 beta was almost identical in all animals. In a separate study intraperitoneal infusion of the same dose of IL-1 beta (1 microgram/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-1 beta (1 microgram 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

Chronic effects of interleukin-1 beta on fever, oxygen consumption and food intake in the rat.

Chronic subcutaneous infusion (from osmotic minipumps) of IL-1 beta (1 microgram/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 microgram, sc) of IL-1 beta was almost identical in all animals. In a separate study intraperitoneal infusion of the same dose of IL-1 beta (1 microgram/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-1 beta (1 microgram 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

Adrenalectomy reverses the impaired pyrogenic responses to interleukin-beta in obese Zucker rats.

Interleukin-1 is an important endogenous pyrogen which stimulates thermogenesis in normal animals by a central action which is dependent on release of corticotrophin releasing factor (CRF). Central injection of murine recombinant interleukin-1 beta (IL-1 beta, 5 ng) in conscious lean (+/?) Zucker rats produced significant increases in resting oxygen consumption (VO2, 26 per cent), colonic temperature (1.3 degrees C) and thermogenic activity (mitochondrial GDP binding) of brown adipose tissue (BAT, 24 per cent). In contrast, genetically obese (fa/fa) Zucker rats showed nonsignificant changes in VO2 (4 per cent), temperature (0.5 degrees C) and BAT activity (0 per cent). Bilateral surgical adrenalectomy (ADX) dramatically enhanced the effects of IL-1 beta on VO2 (45 per cent) body temperature (1.8 degrees C) and BAT activity (44 per cent) in obese mutants, but only slightly increased responses in lean rats. These data suggest that impaired responses to IL-1 beta in obese mutants may be due to inhibitory actions of glucocorticoids on either prostaglandin synthesis or CRF release within the hypothalamus