THE IN-VITRO EFFECTS OF INTERFERON-GAMMA, INTERFERON-ALPHA, AND TUMOR-NECROSIS-FACTOR-ALPHA ON ERYTHROID BURST-FORMING UNIT GROWTH IN PATIENTS WITH NONLEUKEMIC MYELOPROLIFERATIVE DISORDERS

We have studied the effects of interferons gamma (IFN-gamma) and alpha (IFN-alpha), and tumour-necrosis factor-alpha (TNF) on circulating 14 -day erythroid progenitor cell (BFU-E) growth in vitro from patients w ith non-leukaemic myeloproliferative disorders (MPD) compared with nor mal controls. IFN-gamma (1000 U/ml) inhibited BFU-E growth in all cont rols studied (mean growth +/- SE = 61 % +/- 6 %, n = 10). In 7 of 11 M PD studied there was no inhibition, and in some cases clear enhancemen t of BFU-E growth by IFN-gamma. When cultured in the presence of recom binant erythropoietin (rEpo) 1 U/ml, both IFN-alpha and TNF (at 100 an d 1000 U/ml) produced a similar degree of inhibition of BFU-E growth i n MPD and controls. The inhibition by 100 U/ml IFN-alpha was abrogated , partially in controls but completely in MPD, by increasing the dose of rEpo to 5 U/ml. Similarly, the increase in rEpo dose enhanced BFU-E growth in cultures with 100 U/ml TNF, but had little effect on cultur es containing 1000 U/ml of either IFN-alpha or TNF. The aberrant in vi tro response to IFN-gamma demonstrated in some of these patients may b e of relevance to the pathophysiology of MPD. These results fail to de monstrate a differential in vitro effect for IFN-alpha on MPD BFU-E gr owth compared with controls and suggest that the in vitro suppression of haemopoiesis by IFN-alpha when used in MPD treatment is non-specifi c.