INVOLVEMENT OF PROSTAGLANDINS IN CACHEXIA INDUCED BY T-CELL LEUKEMIA IN THE RAT

We have previously demonstrated that experimentally induced T-cell leu kemia in the rat results in a rapid and severe cachexia. This weight l oss is largely due to a reduction in food intake, but is also accompan ied by inappropriately high rates of energy expenditure. Increases in resting oxygen consumption (Vo(2)) of 25% to 35% above the levels of p air-fed animals were observed over the period of weight loss, The pres ent study investigated the possible involvement of prostaglandins in t he cachexia induced by T-cell leukemia in the rat, Acute systemic inje ction of the cyclo-oxygenase inhibitors (indomethacin 1 mg/kg or flurb iprofen 1 mg/kg intraperitoneally [IP]) significantly reduced (by 14% and 10%, respectively) the increase in metabolic rate and also reverse d the elevated body temperature of leukemic animals. Intracerebroventr icular (ICV) injection of indomethacin (0.2 mg/kg) had only modest eff ects on the increase in temperature or hypermetabolism of leukemic ani mals, Long-term daily injection of indomethacin or flurbiprofen (1 mg/ kg/d IF) had no significant effect on food intake or body weight of le ukemic animals, and neither treatment significantly affected disease s tatus. Indomethacin significantly reduced the decline in epididymal fa t pad weight of leukemic animals. These data indicate that prostagland ins, produced peripherally, are involved in the acute hypermetabolism associated with T-cell leukemia, but have little or no effect on the h ypophagia or body weight loss of leukemic rats. Copyright (C) 1997 by W.B. Saunders Company.