This laboratory has been focusing its efforts on the role of lymphokines and cytokines in hematopoiesis and immune system development. Specifically, we have focused on 1) the biochemical characterization of a lymphokine produced by T cells which stimulates B cells to proliferate and 2) the role of specific lymphokines (i.e. IL 1, CSFs) and cytokines (i.e. TNF) in the protection of bone marrow from lethal doses of irradiation. A high molecular weight lymphokine produced by lectin stimulated T lymphocytes that stimulates B cell proliferation has been characterized and highly purified. This BCGF was free of interleukin 1 and 2 (IL 1 and 2) activities, but could induce B cells to proliferate and to express receptors for IL 2. This lymphokine could also support the growth of BCL 1 cells, a unique property of BCGF-II and could augment the proliferation of a large granular lymphocyte line (YT), several EBV +B cell lines and murine thymocytes. In collaboration with scientists at AFRRI we have demonstrated that in vivo administration of recombinant IL 1 beta or IL 1 alpha, 20 hrs prior to lethal doses of irradiation, is protective. Mice pretreated with IL 1 do show a partial recovery in the number of nucleated bone marrow cells and show evidence of increased erythropoiesis by colony forming assays (CFU-E), whereas there is no such recovery in untreated control mice. Bone marrow from IL 1 treated mice demonstrated increased proliferation when subquently cultured for 3 days with GM-CSF. In contrast, administration of several recombinant lymphokines that are induced by IL 1, namely GM-CSF, IL 2 and immune interferon, 20 hrs and 3 hrs before irradiation had no protective or proliferative effect. Prostaglandins are also not effective. Although neither G-CSF nor CM-CSF were effective by themselves, these CSF's in combination with suboptimal doses of IL 1 had synergistic radioprotective effects. Finally TNF, although not as potent as IL 1, also was observed to be radioprotective by itself. IL 1 and TNF together yielded additive effects, suggesting that their mechanism of radioprotection differs.
