Possible involvement of tumor necrosis factor alpha in radiation-induced hyperthermia in rats

Exposure of rats to 1-15 Gy of 60Co gamma radiation induces hyperthermia. Because tumor necrosis factor alpha/cachectin (TNF-alpha) is considered to be an important mediator of the biological response to ionizing radiation, its role in radiation-induced hyperthermia was investigated; in addition, the levels of TNF-alpha in serum before and after radiation exposure were determined. Male Sprague-Dawley rats weighing 250-300 g were irradiated with gamma rays from a 60Co source (10 Gy, 10 Gy/min). Irradiation increased the levels of TNF-alpha in serum. Intraperitoneal (i.p.) doses of 10-50 microg/kg of recombinant human TNF-alpha (hTNF-alpha) induced hyperthermia; i.p. administration of 1-3 mg/kg of indomethacin, an inhibitor of prostaglandin synthesis, or 10-50 microg/kg of polyclonal rabbit anti-human TNF-alpha (anti-hTNF-alpha) attenuated the hyperthermia induced by 30 microg/kg of hTNF-alpha or exposure to 10 Gy of gamma rays. These results suggest that irradiation increases TNF-alpha in serum and that TNF-alpha is involved in gamma-radiation-induced hyperthermia. TNF-alpha and gamma-radiation-induced hyperthermia are mediated by prostaglandins.