Radioprotection with Interleukin-1: Comparison with Other Cytokines

Abstract

Murine IL-1α and human IL-1α and IL-1β protect mice from lethal effects of radiation-induced hematopoietic syndrome. A single 100 ng dose of human IL-1α conferred protection, provided it was administered to C57BL/6 and DBA/1 mice 20 hr before irradiation with an LD100/30 dose, with a DRF of 1.25 and 1.2, respectively. Studies of possible mechanisms of radioprotection by IL-1 showed that radioprotection of LD100/30 irradiated mice could not be induced with IL-2, IFN-γ, or GM-CSF. Radioprotection with IL-1 did not depend on the release of prostaglandins, since indomethacin did not diminish survival of IL-1-treated mice. Unlike C57BL/6 and DBA/1 mice, C3H/HeJ mice were not protected from lethal irradiation by IL-1. Nevertheless, both high-responder C57BL/6 and low-responder C3H/HeJ strains, treated with IL-1, develop similarly enhanced levels of acute phase proteins: metallothionein and ceruloplasmin, with known radioprotective abilities. Therefore, the observed differences in radioprotection with IL-1 in murine strains probably cannot be attributed to differences in levels of these scavenging metalloproteins. In contrast, striking differences were observed in the recovery of bone marrow cells after lethal and midlethal irradiation, in that the recovery of total nucleated bone marrow cells and specifically CFU-Es was much greater in C57BL/6 than in C3H/HeJ mice 9 to 12 days following irradiation. However, the radioprotective effect of IL-1 was similar following sublethal irradiation of the two strains when recovery of endogenous hematopoietic splenic colonies was compared. Consequently, IL-1 can protect C3H/HeJ mice against sublethal but not lethal doses of irradiation. Although much remains to be learned about the mechanism by which IL-1 exerts its radioprotective effect, IL-1 treatment, as is the case for many radioprotective agents, induces recovery of erythropoiesis.