PROTECTION OF HEMATOPOIETIC PROGENITORS FROM ULTRAVIOLET-C BY INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR-ALPHA

Interleukin-l (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can p rotect hematopoietic progenitors from the toxicity of 4-hydroperoxycyc lophosphamide (4-HC) and gamma radiation, We hypothesize that IL-1 and TNF-alpha may be inducing a universal stress reaction in hematopoieti c progenitors, In this study, we examined their protective effects aga inst ultraviolet C (UVC) compared with that seen against 4-HC using co lony formation assays and flow cytometric analysis, We demonstrated th at 20 h preincubation with IL-1 or TNF-alpha or both protected normal hematopoietic colony-forming cells (CFCs) from UVC, Colony formation a ssays and flow cytometric analysis of the cells protected from either 4-HC or WC revealed that similar proportions of hematopoietic progenit ors are protected in the IL-1 and TNF-alpha group in comparison to con trol, Furthermore, at least 20 h of preincubation with the two cytokin es was needed for optimal protection, The addition of 2 mu g/ml cycloh eximide, 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 U VC as well as from 4-HC and gamma radiation, and, therefore, a global response to DNA damaging treatments induced by IL-l and TNF-alpha need s to be further investigated.