Involvement of prostaglandins in cachexia induced by T-cell leukemia in the rat

We have previously demonstrated that experimentally induced T-cell leukemia in the rat results in a rapid and severe cachexia. This weight loss is largely due to a reduction in food intake, but is also accompanied by inappropriately high rates of energy expenditure. Increases in resting oxygen consumption (VO2) of 25% to 35% above the levels of pair-fed animals were observed over the period of weight loss. The present study investigated the possible involvement of prostaglandins in the cachexia induced by T-cell leukemia in the rat. Acute systemic injection of the cyclo-oxygenase inhibitors (indomethacin 1 mg/kg or flurbiprofen 1 mg/kg intraperitoneally [IP]) significantly reduced (by 14% and 10%, respectively) the increase in metabolic rate and also reversed the elevated body temperature of leukemic animals. Intracerebroventricular (ICV) injection of indomethacin (0.2 mg/kg) had only modest effects on the increase in temperature or hypermetabolism of leukemic animals. Long-term daily injection of indomethacin or flurbiprofen (1 mg/kg/d IP) had no significant effect on food intake or body weight of leukemic animals, and neither treatment significantly affected disease status. Indomethacin significantly reduced the decline in epididymal fat pad weight of leukemic animals. These data indicate that prostaglandins, produced peripherally, are involved in the acute hypermetabolism associated with T-cell leukemia, but have little or no effect on the hypophagia or body weight loss of leukemic rats.