In vitro improvement of bone marrow-derived hematopoietic colony formation in HIV-positive patients by alpha-D-tocopherol and erythropoietin.
The majority of patients with progressive HIV infection develop a severe hematopoietic failure which is aggravated by the hematotoxic effect of azidothymidine (AZT) treatment. Since it was shown in a mouse model that alpha-D-tocopherol (vitamin E derivative) antagonizes the inhibitory influence of AZT on the growth of burst-forming units-erythrocyte (BFU-E), it was the aim of this study to investigate whether alpha-D-tocopherol and high dosages of erythropoietin (EPO) increase the hematopoietic colony-forming capacity of bone marrow cells from patients with progressive HIV disease and especially if they reverse the inhibitory effects of AZT. The data demonstrate that tocopherol (1-100 mumol/l) significantly increases the growth of BFU-E and colony-forming units granulocyte-monocyte (CFU-GM) from HIV-infected patients. This stimulatory effect is dose-dependent (maximum at 30-100 mumol/l) and only occurs when the agent is present from the beginning of the cultures. EPO (5-10 U/ml) also augments the numbers of BFU-E from HIV-infected patients. Tocopherol equally ameliorates the growth of BFU-E and CFU-GM from the HIV-positive cohort in the presence of AZT (10-100 mumol/l). For healthy controls, no such increase was observed, either with tocopherol or with higher dosages of EPO. In conclusion, both tocopherol and EPO partially reverse the myelosuppressive action of AZT in HIV-positive patients.
University of Frankfurt/Main, Germany.
R G
RG
Geissler
A
A
Ganser
O G
OG
Ottmann
P
P
Gute
A
A
Morawetz
P
P
Guba
E B
EB
Helm
D
D
Hoelzer
D000328:Adult; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D014810:Vitamin E / Q000494:pharmacology*; D015215:Zidovudine / Q000037:antagonists & inhibitors / Q000627:therapeutic use
D004921:Erythropoietin; D014810:Vitamin E; D015215:Zidovudine