Central effects of TNF alpha on thermogenesis and fever in the rat.

Intracerebroventricular (icv) injection of purified recombinant human tumour necrosis factor alpha (TNF alpha, 4-8 micrograms) in conscious rats, produced increases in colonic temperature (1.0 degrees C) and resting oxygen consumption (VO2, 14%) which were maximal after 80-90 minutes. Pretreatment with propranolol (10 mg/kg s.c.) significantly inhibited the rise in VO2, and prevented the increase in body temperature. Icv injection of an antagonist to corticotropin releasing factor (alpha-helical CRF 9-41, 25 micrograms), which prevents the pyrogenic and thermogenic actions of interleukin-1 beta, did not influence the effects of TNF alpha on temperature or VO2. Injection of a fragment of TNF alpha (113-130 amino acid sequence) did not affect body temperature or VO2. TNF alpha injection (icv) significantly increased brown adipose tissue (BAT) in vitro mitochondrial GDP binding, and this effect was slightly inhibited, but not prevented, by surgical denervation of the tissue, and was unaffected by pretreatment with alpha-helical CRF 9-41. These data indicate that TNF alpha can stimulate thermogenesis by a direct central action. The effects are largely, but not totally, dependent on the sympathetic nervous system but, unlike the thermogenic actions of interleukin they do not require release of CRF.