title: The in vitro effects of interferon-gamma, interferon-alpha, and tumour-necrosis factor-alpha on erythroid burst-forming unit growth in patients with non-leukaemic myeloproliferative disorders.
abstract: 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 with non-leukaemic myeloproliferative disorders (MPD) compared with normal controls. IFN-gamma (1000 U/ml) inhibited BFU-E growth in all controls studied (mean growth +/- SE = 61% +/- 6%, n = 10). In 7 of 11 MPD studied there was no inhibition, and in some cases clear enhancement of BFU-E growth by IFN-gamma. When cultured in the presence of recombinant erythropoietin (rEpo) 1 U/ml, both IFN-alpha and TNF (at 100 and 1000 U/ml) produced a similar degree of inhibition of BFU-E growth in 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 cultures containing 1000 U/ml of either IFN-alpha or TNF. The aberrant in vitro response to IFN-gamma demonstrated in some of these patients may be of relevance to the pathophysiology of MPD. These results fail to demonstrate a differential in vitro effect for IFN-alpha on MPD BFU-E growth compared with controls and suggest that the in vitro suppression of haemopoiesis by IFN-alpha when used in MPD treatment is non-specific.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, London, U.K.
authors.forename: E J
authors.initials: EJ
authors.lastname: Kanfer
authors.forename: C M
authors.initials: CM
authors.lastname: Price
authors.forename: A A
authors.initials: AA
authors.lastname: Gordon
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D009196:Myeloproliferative Disorders / Q000503:physiopathology*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007371:Interferon-gamma