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.