In vitro effects of stem-cell factor or interleukin-3 on myelosuppression associated with AIDS.
OBJECTIVE
To determine whether the early-acting hematopoietic growth factors stem-cell factor (SCF) or interleukin-3 (IL-3), are able to overcome the bone-marrow suppressive effects of cytokines or drugs involved in the hematologic abnormalities that accompany HIV-1 infection.


METHODS
In vitro colony formation assays of normal human bone-marrow cells exposed to the myelosuppressive drugs, zidovudine, interferon-alpha (IFN-alpha) and ganciclovir, or the myelosuppressive cytokines, tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta (TGF-beta), implicated in HIV dysmyelopoiesis.


RESULTS
SCF (10 ng/ml) enhanced the numbers of erythroid (BFU-E) colonies in the presence of zidovudine or ganciclovir (P < 0.05) and myeloid [colony-forming unit granulocyte macrophage (CFU-GM)] colonies in the presence of ganciclovir or IFN-alpha (P < 0.05) relative to controls. IL-3 (10 ng/ml) also improved erythroid colony numbers in the presence of zidovudine (P < 0.05) and CFU-GM in the presence of IFN-alpha (P < 0.05). Neither factor consistently altered the inhibition of TGF-beta or TNF-alpha. The 50% inhibitory concentration (IC50) of the myelosuppressive agents was altered in only one setting, using IL-3 in the presence of zidovudine.


CONCLUSIONS
These data suggest that SCF or IL-3 may have a therapeutic application in overcoming hematopoietic abnormalities associated with drugs commonly used in the care of AIDS patients. However, they may have less capacity to overcome the bone-marrow inhibitory effects of the endogenous cytokines TNF-alpha and TGF-beta.
Scadden
D T
DT
Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Wang
A
A
Zsebo
K M
KM
Groopman
J E
JE
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D001855:Bone Marrow Diseases / Q000139:chemically induced*; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D008264:Macrophages; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D016298:Hematopoietic Cell Growth Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015774:Ganciclovir