In vitro effects of recombinant TNF-alpha binding protein (rTBP-1) on hematopoiesis of HIV-infected patients.
Tumor necrosis factor-alpha (TNF-alpha) is believed to contribute to the hematopoietic failure often observed in patients with AIDS. Soluble TNF receptors (sTNFR) compete for TNF-alpha with cell surface receptors and thus may block its activity. The effect of the p55 sTNFR (recombinant TNF-binding protein-1 [rTBP-1]) on the clonogenic growth of hematopoietic progenitor cells from 27 HIV-infected patients was evaluated in comparison with 11 normal study subjects. Peripheral blood-derived, myelopoietic (i.e., granulomonocytic colony-forming cells [GM-CFC]) and erythropoietic (i.e, burst-forming unit, erythroid [BFU-E]) colonies were grown in 10-day semisolid cultures with increasing concentrations of rTBP-1. Significantly, dose-dependent increases occurred in GM-CFC from 17 of 21 AIDS patients and 12 of 21 in BFU-E at rTBP-1 concentrations of 1microg/ml to 25 microg/ml. In contrast, rTBP-1 failed to induce any appreciably increased colony formation in normal cell cultures. In 6 patients treated with highly active antiretroviral treatment (HAART), TBP-1 alone did not demonstrate the in vitro hematopoiesis-enhancing effect. This study may provide an initial step in development of therapeutic use of TBP as a TNF-alpha antagonist in HIV-infected patients who do not benefit sufficiently from antiretroviral treatment, and in other conditions in which increased levels of TNF-alpha may contribute to hematopoietic deficiencies.
Kaplan Medical Center, Rehovot, Israel.
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S
Gradstein
T
T
Hahn
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Y
Barak
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Malach
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M
Revel
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Bentwich
Z T
ZT
Handzel
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004306:Dose-Response Relationship, Immunologic; D015672:Erythroid Precursor Cells / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha