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Recombinant human interleukin 1β (IL 1β) inhibits growth of B16 melanoma in syngeneic C57BL/6 mice in a dose-dependent manner when given intratumorally, intradermally, or intramuscularly over a period of 5 to 7 days. Inhibition of tumor growth was rapid and measurable within 3 days after the initial injection and occurred regardless of the route of injection. However, only intratumoral (ITU) injections of IL 1β resulted in greater than 90% inhibition in tumor growth. This enhanced inhibition of tumor growth was not dependent on T or NK cells since inhibition of tumor growth occurred in nude and Beige mice. Also, a profound lymphopenia occurred in mice receiving IL 1β. Inhibition of tumor growth did correlate with an increase in the number of polymorphonuclear leukocytes (PMN's) in the circulation. However, only ITU injections of IL 1β increased the number of PMN's within the tumors. IM injections of IL 1β, while increasing the number of PMN's in the circulation, did not increase the influx of PMN's into the tumors. Furthermore, the transfer of PMN's directly into B16 tumors caused a 49% reduction in tumor growth without the presence of IL 1β. These results suggest that in vivo, PMN's may effectively control the growth of tumors and that IL 1β may increase this effectiveness by increasing the number of PMN's in the circulation and by locally stimulating the production of chemotactic factors for PMN's within the tumor.

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.