Exposure of rats to 1-15 Gy of60 Co γ radiation induces hyperthermia. Because tumor necrosis factor α/cachectin (TNF-α) 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-α in serum before and after radiation exposure were determined. Male Sprague-Dawley rats weighing 250-300 g were irradiated with γ rays from a60 Co source (10 Gy, 10 Gy/min). Irradiation increased the levels of TNF-α in serum. Intraperitoneal (i.p.) doses of 10-50 μg/kg of recombinant human TNF-α (hTNF-α) induced hyperthermia; i.p. administration of 1-3 mg/kg of indomethacin, an inhibitor of prostaglandin synthesis, or 10-50 μg/kg of polyclonal rabbit anti-human TNF-α (anti-hTNF-α) attenuated the hyperthermia induced by 30 μg/kg of hTNF-α or exposure to 10 Gy of γ rays. These results suggest that irradiation increases TNF-α in serum and that TNF-α is involved in γ-radiation-induced hyperthermia. TNF-α and γ-radiation-induced hyperthermia are mediated by prostaglandins.

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