Anorexia, weight loss and increased plasma interleukin-6 caused by chronic intracerebroventricular infusion of interleukin-1beta 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 disease. In the present study, the effects of chronic exposure of the CNS to interleukin-1beta (IL-1beta) 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-1beta for 4 days. Food intake and body weight were determined daily during the 4-day infusion period and plasma IL-6 and corticosterone concentrations were determined from plasma collected postinfusion. Chronic i.c.v. infusion of IL-1beta resulted in a chronic reduction in food intake. Rats infused i.c.v. with IL-1beta ate 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. Intracerebroventricular infusion of IL-1beta also caused an immediate and substantial loss of body weight that was sustained throughout the infusion period. In addition, rats infused with IL-1beta had plasma levels of IL-6 double those of vehicle controls (401 pg/ml vs. 185 pg/ml). Plasma corticosterone concentrations were similar between treatments. These results suggest that chronic exposure of the CNS to cytokines such as IL-1beta may be sufficient to induce anorexia and cachexia.
Finck
B N
BN
Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
Johnson
R W
RW
D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss / Q000187:drug effects*
D007375:Interleukin-1; D015850:Interleukin-6; D003345:Corticosterone