ANOREXIA, WEIGHT-LOSS AND INCREASED PLASMA INTERLEUKIN-6 CAUSED BY CHRONIC INTRACEREBROVENTRICULAR INFUSION OF INTERLEUKIN-1-BETA IN THE RAT

Pro-inflammatory cytokines produced in the central nervous system (CNS ) have been suggested to have a role in the anorexia and cachexia of d isease. In the present study, the effects of chronic exposure of the C NS to interleukin-1 beta (IL-1 beta) on several indicators of cachexia were studied. Rats were prepared with an intracerebroventricular (i.c .v.) cannula and an osmotic minipump that delivered vehicle or 1.56 ng /h recombinant murine IL-1 beta for 4 days. Food intake and body weigh t were determined daily during the 4-day infusion period and plasma IL -6 and corticosterone concentrations were determined from plasma colle cted postinfusion. Chronic i.c.v. infusion of IL-1 beta resulted in a chronic reduction in food intake. Rats infused i.c.v. with IL-1 beta a te less food each day compared to vehicle controls and, at the end of the 4-day infusion period, consumed an average of 17.2 g less. Intrace rebroventricular infusion of IL-1 beta also caused an immediate and su bstantial loss of body weight that was sustained throughout the infusi on period. In addition, rats infused with IL-1 beta had plasma levels of IL-6 double those of vehicle controls (401 pg/ml vs. 185 pg/ml). Pl asma corticosterone concentrations were similar between treatments. Th ese results suggest that chronic exposure of the CNS to cytokines such as IL-1 beta may be sufficient to induce anorexia and cachexia. (C) 1 997 Elsevier Science B.V.