INTERFERON-GAMMA (IFN-GAMMA) AS A POTENTIAL RADIO-PROTECTANT AND CHEMO-PROTECTANT

Interferons (IFN) have had increasing clinical usage in the treatment of a variety of disorders, at times being used in combination with che mo- or radiotherapy. However, interferons may have inhibitory effects on hematopoietic stem cell proliferation and the effects of this cytok ine's use on long-term hematologic function have not been studied. We performed the competitive repopulation assay in the murine system, usi ng cells exposed to irradiation or single-dose chemotherapy with or wi thout concomitant IFN-gamma use. IFN-gamma alone had no deleterious ef fects on hematopoietic stem cell productivity. We measured the repopul ating ability of exhaustible multilineage precursors that were present at early stages of marrow repopulation after competitive repopulation (30 days). These progenitors were minimally impacted by cyclophospham ide (CTX) with or without IFN-gamma. Irradiation (XRT) and CTX alone p roduced significant repopulating defects in the most primitive hematop oietic stem cell, PHSC. Addition of IFN to either treatment regimen re sulted in protection of PHSC, with improved repopulating ability, alth ough the levels of donor marrow reached control levels only when CTX a nd IFN were used together. The results of multiple use of IFN with che motherapy must be studied further, but IFN may offer hematologic radio - and chemoprotection, in addition to its antitumor properties in clin ical protocols for treatment of cancers. Am. J. Hematol. 58:218-223, 1 998. (C) 1998 Wiley-Liss, Inc.