In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1β: I. Tumor inhibition parallels lymphocyte-activating factor activity of interleukin 1β proteins

Abstract

Seven daily intratumoral injections of human recombinant interleukin 1β (rHu-IL 1β) 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 1β (intramuscular, intraperitoneal, intradermal) inhibited tumor growth but to a lesser degree (27% to 50%). Two different rIL 1βs, one a mutein of rHu-IL 1β (Glu-4) and the other one murine IL 1β (rM-IL 1β), were tested in the tumor inhibition model. rM-IL 1β inhibited tumor growth at lower concentrations than did rHu-IL 1β and also had enhanced IL 1 activity in the thymocyte assay in vitro. The mutein of rHu-IL 1β (Glu-4) had significantly reduced in vitro IL1 activity and did not inhibit tumor growth. No cytotoxic or cytostatic effects of rHu-IL 1β were observed in in vitro assays. These results suggest that rHu-IL 1β 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 1β.