Protection of hematopoietic progenitors from ultraviolet C by interleukin-1 and tumor necrosis factor-alpha.

Abstract

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can protect hematopoietic progenitors from the toxicity of 4-hydroperoxycyclophosphamide (4-HC) and gamma radiation. We hypothesize that IL-1 and TNF-alpha may be inducing a universal stress reaction in hematopoietic progenitors. In this study, we examined their protective effects against ultraviolet C (UVC) compared with that seen against 4-HC using colony formation assays and flow cytometric analysis. We demonstrated that 20 h preincubation with IL-1 or TNF-alpha or both protected normal hematopoietic colony-forming cells (CFCs) from UVC. Colony formation assays and flow cytometric analysis of the cells protected from either 4-HC or UVC revealed that similar proportions of hematopoietic progenitors are protected in the IL-1 and TNF-alpha group in comparison to control. Furthermore, at least 20 h of preincubation with the two cytokines was needed for optimal protection. The addition of 2 micrograms/ml cycloheximide, a protein synthesis inhibitor, during the 20 h preincubation completely abolished the protection observed for CFCs. In conclusion, IL-1 and TNF-alpha can protect normal hematopoietic progenitors from UVC as well as from 4-HC and gamma radiation, and, therefore, a global response to DNA damaging treatments induced by IL-1 and TNF-alpha needs to be further investigated.