Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF and IFN gamma.

Immunomodulatory agents are radioprotective when administered to animals prior to irradiation. The mechanisms for this radioprotection have as yet not been determined, but may involve endogenously released cytokines. We have recently demonstrated that murine IL-1 is radioprotective in mice (Neta et al. J. Immunol., 136, 2483, 1986). In this study we have further explored this effect and investigated whether the radioprotective effect of IL-1 is mediated by other cytokines. Optimal radioprotection with IL-1 was obtained with administration 20 hr prior to irradiation and was greatly reduced with administration 45 or 4 hr before or 1 hr after irradiation with 950 cGy, an LD100/30 dose. The dose reduction factor (DRF) measured by LD50/30 was 1.25 for C57B1/6 mice. The presence of a lag period in IL-1 induced radioprotection suggests that the effect of IL-1 may be indirect. The hypothesis that IL-1 may act by inducing the release of other cytokines was tested in part by two approaches: Assays for circulating IFN and CSF. High titers of CSF were present at 3 and 6 hrs and declined at 24 hrs after administration of 0.1 microgram of IL-1, a dose radioprotective in mice. Assays for IFN in the same sera were negative. Direct administration of recombinant IFN-gamma, GM-CSF, or IL-2 prior to LD100/30 irradiation. Using a wide range of doses of these cytokines delivered 20 or 3 hr prior to irradiation, no significant radioprotective effect was observed.