Anti-cytokine antibodies reveal the interdependence of pro-inflammatory cytokines in protection from lethal irradiation. (Reannouncement with new availability information)

Ionizing radiation is particularly damaging to lymphoid and hematopoietic tissues, leading to anemia and decreased resistance to opportunistic infections, often resulting in death. Administration prior to irradiation of immunostimulatory/ inflammatory agents that enhance host`s defenses was shown several decades ago also to enhance survival. It is now known that virtually all of the pathophysiological effects elicited by such adjuvants are mediated by cytokines, hormone-like polypeptides that transmit signals from one cell to another. These include pluripotent inflammatory cytokines: IL 1, TNF, LIF, and IL 6, hematopoietic growth factors (CSF`s), interferons, as well as the immunosuppressive TGFBeta. The cytokines IL 1 and TNF have emerged as particularly important mediators of host defenses. Thus, the earlier findings that these two cytokines can confer radioprotection is consistent with their role in protecting the host from damaging environmental agents. Recently, IL 1 and TNF were shown to be produced by cells following exposure to ionizing radiation. These findings suggested that even endogenously produced cytokines may contribute to recovery from ionizing radiation. This hypothesis was examined using monoclonal antibodies to IL 1 receptor (IL IR) , to TNF, and to IL 6. These antibodies also enabled the authors to evaluate the contribution of IL 1more » and TNF to LPS-induced radioprotection, and the relative contribution and relationship of IL 1, TNF, and IL 6 to one another in radioprotection.« less