MECHANISMS OF CACHEXIA INDUCED BY T-CELL LEUKEMIA IN THE RAT

Body wasting (cachexia) is a common feature of cancer and a major caus e of morbidity and mortality. The mechanisms underlying cachexia are l argely unknown, and studies in experimental animals have focused mainl y on solid tumors. Therefore, the objective of the present study was t o quantify and investigate cachexia in experimentally induced T-cell l eukemia in the rat. Induction of leukemia by serial passage (injection of cervical lymph node suspension) resulted in a rapid increase in wh ite blood cell (WBC) count, hypertrophy of the spleen (by day 11), and severe morbidity within 17 to 18 days. Body weight gain and food inta ke declined steadily in leukemic animals from day 12, although weight loss was significantly greater in pair-fed, nonleukemic animals. Howev er, leukemic rats had a lower body fat content and higher water conten t than pair-fed animals on day 18, so the measurement of body weight s ignificantly underestimated the severity of cachexia. Resting oxygen c onsumption (VO2), measured during the light phase, declined in pair-fe d animals from day 13, but was elevated in leukemic rats on days 12 to 18 by 25% (P < .05, one-way ANOVA) compared with pair-fed rats and by 7% (P < .05, one-way ANOVA) relative to free-feeding controls. Hyperm etabolism was associated with an increase in brown adipose tissue (BAT ) activity (74% and 89%, respectively, P < .05, one-way ANOVA) in leuk emic rats compared with control and pair-fed groups. Effects of leukem ia on VO2 and BAT were prevented by administration of the adrenergic a ntagonist, propranolol. These results indicate that T-cell leukemia in the rat results in rapid and severe cachexia, which is largely due to marked hypophagia, but is also accompanied by inappropriately high ra tes of energy expenditure that are mediated by sympathetic activation of BAT thermogenesis. (C) 1996 by W.B. Saunders Company.