The in vivo effect of recombinant human interleukin-1 receptor antagonist on spleen colony forming cells after radiation induced myelosuppression.

It is known that IL-1 influences in vitro growth of hemopoietic stem cells (HSC) in a synergistic pattern with hemopoeitic growth factors and has a radioprotective activity in vivo. It is possible that these effects of IL-1 on HSC involve a previous up-regulation of IL-1 receptors. In this work the effects of rhIL-1Ra treatment on the proliferation of subpopulations of HSC (CFU-Sd12 and CFU-Sd8) were investigated in normal and irradiated mice (2 Gy, X rays). CBA/H mice were treated with two i.p. injections of rhIL-1Ra (2 x 50 micrograms per mouse) seventeen hours and two hours before sacrifice on day three after irradiation. Normal, non-irradiated control animals were treated in the same way. The proliferation rate of bone marrow CFU-Sd12 and CFU-Sd8 was determined by the in vitro Ara-C suicide technique. In normal mice, treatment with rhIL-1Ra did not significantly influence the number and proliferation rate of CFU-Sd12 and CFU-Sd8. In the regenerating bone marrow of irradiated animals the cycling of CFU-Sd12 and CFU-Sd8 was increased. In irradiated animals, rhIL-1Ra treatment clearly reduced the cycling of CFU-Sd12 but not significantly alter CFU-Sd8. Our results indicate a role of IL-1 in the regulation of sustained proliferation of HSC in regenerating bone marrow.