Effects of four species of interferon-alpha on cultured erythroid progenitors from congenital dyserythropoietic anaemia type I

The in vitro effects of interferon (IFN)-alpha on erythroid progenitor cell s derived from the peripheral blood of five patients with congenital dysery thropoietic anaemia (CDA) type I and seven healthy adults were studied. Fic olhypaque-separated mononuclear cells were cultured for 14 d in StemGEM-1d medium with 0, 1, 10 and 100 U/ml of recombinant IFN-alpha(2a), recombinant IFN-alpha(2b), the genetically engineered hybrid molecule IFN-alpha(1-)8 o r the laboratory designed molecule IFN-alpha(consensus). Erythroid bursts a nd colonies were counted, picked and processed for electron microscopy. In the experiments employing IFN-alpha(2a) there were no differences in the nu mbers of erythroid bursts or colonies between four patients with CDA type I and seven healthy adults. All five patients with CDA type I showed the 'Sw iss-cheese' ultrastructural abnormality of the heterochromatin in a proport ion of the erythroblasts when the progenitor cells were cultured in the abs ence of added IFN-alpha. A statistically significant reduction in the propo rtion of erythroblasts showing the 'Swiss-cheese' defect was seen when the erythroid progenitors were cultured in the presence of 0.01-0.5 U/ml IFN-al pha(2a) (five patients), or 0.1 U/ml of IFN-alpha(2b), (two patients). In c ontrast, no reduction was seen in cultures containing 0.1-100 U/ml of eithe r IFN-alpha(1-8) or IFN-alpha(consensus) or 20 mu M hydroxyurea (two patien ts). The partial correction of the 'Swiss-cheese' abnormality by low concen trations of IFN-alpha(2a) in vitro provides an experimental model with whic h the mechanisms underlying the haematological response that occurs after t he in vivo administration of this species of IFN-alpha may be investigated.