Radio- and chemoprotection of bone marrow cells by opposite cell cycle-acting cytokines.

Cytokines such as interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), stem cell factor (SCF), and interleukin-12 (IL-12), among others, are presently known to exert a radioprotective effect on bone marrow (BM) precursor cells. IL-1, TNF-alpha, transforming growth factor-beta (TGF-beta), and macrophage inflammatory protein-1 alpha (MIP-1alpha) exert a chemoprotective effect on BM cells, while a putative role of IL-12 in this effect is still unknown. IL-1, SCF, and IL-12 are known to promote BM precursor cell cycling. Conversely, TNF-alpha, MIP-1alpha, and TGF-beta, the latter a radiosensitizer, induce cycle arrest in these cells. Cycling increases radioprotection, while arrest reduces chemical damage. IL-1 and TNF-alpha are unique in their ability to induce detoxifying mechanisms. The present communication overviews these effects. It also proposes a model, based on the induction of biochemical detoxifying mechanisms, aiming to explain BM cell radio- and chemoprotection by opposite cell cycle-acting cytokines.