Pre-administration of cytokines, in particular IL 1 can protect mice from lethal doses of irradiation ranging from 900 to 1,200 cGy. IL 1 when administered after irradiation can protect mice up to doses of 1,000 cGy. These beneficial effects of the cytokines were based on the recovery of suppressed hematopoietic tissues. This was substantiated by experiments showing that co-administration of IL 1 along with 10 to the sixth to 10 to the seventh syngeneic bone marrow cells synergistically promoted the survival of mice irradiated with up to 1,500 cGy. IL 1 also enhanced the capacity of allogeneic bone marrow cells to promote survival of mice given doses of radiation ranging from (1,100-1,350 cGy). Long term survivors were chimeric and tolerant to recipient and donor alloantigens, but exhibited immunological competence. These data suggest that IL 1 may prove clinically useful in patients undergoing bone marrow transplantation. The role of cytokines in oncogenesis was also investigated. JB6 is a nontumorigenic murine epidermal cell line which undergoes irreversible phenotypic modification when treated with tumor promoters, such as PMA. JB6 loses anchorage dependence, as measured by colony formation in soft agar, and becomes tumorigenic in nude mice. The induction of transformation by PMA is inhibited by the addition of antipromoters, such as retinoids. TGF-beta also was able to decrease, in a dose dependent manner, the number of colonies induced by PMA. This effect was not due to nonspecific inhibition of growth, since TGF-beta did not inhibit the growth rate of untreated and PMA treated adherent JB6 cells. IFNalpha-beta, IL 6 and IL 1 had no significant effect on colony formation induced by PMA. Moreover, TGF-beta enhances the antipromoting activity of suboptimal concentrations of retinoic acid. Our data suggest that TGF-beta may play a role in the regulation of transformation of JB6 cells.
