Human recombinant interleukin-1 receptor antagonist (hrIL-1ra) enhances the stimulatory effect of interleukin-2 on natural killer cell activity against MOLT-4 target cells.

Interleukin-1 (IL-1) is considered an enhancer of host defence against malignancies. Patients with different diseases, including cancer patients with large tumour burdens, have demonstrated a reduced production of IL-1 from circulating leukocytes, in vitro. There are many naturally occurring substances which inhibit IL-1 activity aspecifically. Recently an interleukin-1 receptor antagonist (IL-1ra) has been discovered, which is secreted by human macrophages and is structurally similar to IL-1 beta (26% homology). The pretreatment of human peripheral blood mononuclear cells (PBMC) with hrIL-1ra (0.25-250 ng/ml) inhibits IL-1 alpha or IL-1 beta and enhances, in a dose-dependent manner, the stimulatory effect of IL-2 on their natural killer (NK) activity against a lymphoid cell line MOLT-4. The enhancing effect of IL-1ra on IL-2 activity was similar to that provoked by IL-1 beta. However, when IL-1ra was used alone without IL-2, no stimulatory effect was found compared with the control. In our data we show that a member of the IL-1 family, IL-1ra, has a significant effect on IL-2-stimulated NK activity against the MOLT-4 cell line. These studies provide new evidence of the biological potential of IL-1ra since this new protein enhances IL-2 activity on NK cells.