INTERLEUKIN-1 (IL-1) RECEPTOR-TYPE-I MEDIATES ANOREXIA BUT NOT ADIPSIA INDUCED BY CENTRALLY ADMINISTERED IL-1-BETA

IL-1 beta induces anorexia and adipsia. Here, we report that intracere broventricular (ICV) pretreatment with an antisense (but not sense) ph osphothio-oligodeoxynucleotide to the IL-1 receptor type I (IL-1RI, 1. 28 mu g or 239 pmol twice daily for 3.5 days before IL-1 beta plus ant isense) inhibits the anorexia, but not the adipsia induced by the ICV administration of 2.0 ng IL-1 beta/rat (a dose that yields estimated p athophysiological concentrations in the cerebrospinal fluid). The mean 2 h food intake decrease in response to IL-1 beta was 5.6% (n = 10) i n the antisense-and 43% in the sense (n = 9)-treated groups; the mean 2 h water intake decrease was 40% in the antisense-and 39% in the sens e-treated groups. The intraperitoneal administration of IL-1RI antisen se, in doses equivalent to those administered centrally, had no effect on the anorexic effect induced by ICV administered IL-1 beta this ind icates a direct action in the central nervous system. The results sugg est that: i) IL-IRI is involved in the short-term anorexigenic, but no t the adipsogenic effect induced by centrally administered IL-1 beta; and ii) the approach presented using antisense strategies is applicabl e to study the molecular basis of IL-1 mediated behaviors. (C) 1997 El sevier Science Inc.