Inhibition by interleukin 1 receptor antagonist of in vivo activities of interleukin 1 in mice

: A polypeptide homologous to IL-1, with antagonistic activity (IL-1ra), has recently been described. Given the pleiotropic activity of interleukin (IL-1) it is important to establish the spectrum of inhibitory activity of IL-1ra on in vivo action of IL-1. We tested the effect of IL-1ra on IL-1 induced lethality in adrenalectomized mice, hypoglycemia, and induction of serum corticosterone and interleukin 6. Administration of IL-1ra (200 micrograms/mouse) protected adrenalectomized mice against the lethal effect of 1 microgram of IL-1. IL-1ra at 20 micrograms/mouse completely blocked induction of IL-6 and markedly inhibited hypoglycemia and increase in serum corticosterone induced by 0.1 micrograms of IL-1. These data indicate that IL-1ra inhibits the action of IL-1 on different target tissues involved in the various actions of IL-1 in vivo