PROTECTIVE EFFECTS OF HUMAN INTERLEUKIN-1 ON HEMATOPOIETIC PROGENITORCELLS FROM L-PHENYLALANINE MUSTARD

The effects of interleukin-1 (IL-1) on protecting both human and murin e bone marrow cells were studied using in vitro clonogenic assays, lon g-term bone marrow cultures and in vivo mouse studies. Incubation with 100 ng/ml human recombinant IL-1 beta for 20 hours prior to a one hou r exposure to L-phenylalanine mustard (L-PAM) provided significant pro tection of bone marrow colony forming cells when compared to bone marr ow cells not exposed to IL-1. Complete inhibition of colony formation was observed above 40 mu M L-PAM in the absence of IL-1 preincubation; whereas, colonies were still detectable in cultures which were initia ted with IL-1-treated bone marrow cells. Similar results demonstrating greater protection with IL-1 incubation from L-PAM were seen when mur ine bone marrow cells were assayed for long-term culture-initiating ce lls. Furthermore, IL-1 protects long-term repopulating hematopoietic s tem cells from L-PAM when studied using an in vivo irradiated mouse as say. In contrast, incubation with IL-1 does not protect colony formati on by K562, KG-1 or HL-60 leukemic cell lines implying that protection by IL-1 may be selective. Finally, the protection observed by IL-1 pr eincubation could be abrogated by incubation with 50 mu M L-buthionine sulfoximine (BSO). This result indicates that IL-1 may increase the a mount of glutathione in hematopoietic cells and be responsible for the observed protection from L-PAM.