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Seven daily intratumoral injections of human recombinant interleukin 1 beta (rHu-IL 1 beta) inhibit the growth of B16 melanoma in syngeneic female C57BL/6 mice. Inhibition was dose dependent and ranged from 36% to 93%. Other routes of injection of rHu-IL 1 beta (intramuscular, intraperitoneal, intradermal) inhibited tumor growth but to a lesser degree (27% to 50%). Two different rIL 1 beta s, one a mutein of rHu-IL 1 beta (Glu-4) and the other one murine IL 1 beta (rM-IL 1 beta), were tested in the tumor inhibition model. rM-IL 1 beta inhibited tumor growth at lower concentrations than did rHu-IL 1 beta and also had enhanced IL 1 activity in the thymocyte assay in vitro. The mutein of rHu-IL 1 beta (Glu-4) had significantly reduced in vitro IL1 activity and did not inhibit tumor growth. No cytotoxic or cytostatic effects of rHu-IL 1 beta were observed in in vitro assays. These results suggest that rHu-IL 1 beta has antitumor activity in vivo that is probably not due to its direct effects on B16 cells but rather is mediated by secondary effects of IL 1 beta.

The anti-tumour properties of interleukin 1β (IL-1β) were examined using an intradermal B16 murine melanoma surgical model. B16 cells were injected intradermally on the right ventral side and surgery was performed on days 10–20 to remove the primary tumours. IL-1β or vehicle was administered prior to surgery for 5–7 consecutive days. In mice which received only injections of vehicle, survival ranged between 0 and 30% when measured on day 120 after implantation of B16 cells. Mice died of metastases and growth of B16 cells in the thoracic lymph nodes. When mice without metastases were rechallenged with viable B16 cells, only one out of 22 mice (5%) failed to develop tumours. No significant immunity to B16 cells was detected in this group of mice. In contrast, in mice which received injections of IL-1β, survival ranged between 70–100% on day 120 after implantation of B16 cells. When IL-1β treated mice were rechallenged with viable B16 cells on day 120, 20 out of 32 (63%) mice failed to develop B16 tumours suggesting that some of these mice had immunity to B16 melanoma cells. Moreover, mice with immunity to B16 cells did develop tumours when injected with another syngeneic tumour, MCA 105. In vitro specific immune responses were also demonstrated in spleen cells and sera from mice treated with IL-1β, but not in the spleen cells or sera of mice that received only vehicle. These results suggest that administration of IL-1β to mice bearing B16 melanomas alters or provokes protective immune responses to B16 melanoma cells which are not normally present in mice bearing B16 tumours.