INTERLEUKIN-1-ALPHA INCREASES SERUM LEPTIN CONCENTRATIONS IN HUMANS

Leptin, the protein product of the ob gene, regulates appetite and bod y weight in animals. Endotoxin and cytokines, induced by endotoxin, in terleukin (IL) 1 and tumor necrosis factor, increase expression of lep tin in mice and hamsters. We measured serum leptin concentrations in p atients with cancer before and after administration of recombinant hum an IL-1 alpha. Fourteen patients received IL-1 alpha at one of three d ose levels (0.03, 0.1, or 0.3 mu g/kg.day) for 5 days. Serum leptin co ncentrations increased in all but two patients within 24 h after the f irst dose. The increase in leptin was correlated directly with IL-1 al pha dose (P = 0.0030). Despite continued administration of IL-1 alpha, serum leptin concentrations returned to pretreatment levels by day 5 of therapy. An increase in serum leptin concentrations may be one mech anism by which anorexia is induced by IL-1 alpha. However, tachyphylax is of the leptin response suggests that other mechanisms also are invo lved.