In vitro effects of recombinant tnf-α binding protein (rTBP- 1) on hematopoiesis of HIV-infected patients

Serge Gradstein, Talia Hahn, Yigal Barak, Leah Malach, Michel Revel, Zvi Bentwich, Zeev T. Handzel

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Tumor necrosis factor-alpha (TNF-α) is believed to contribute to the hematopoietic failure often observed in patients with AIDS. Soluble TNF receptors (sTNFR) compete for TNF-α 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 1μ/ml to 25 μ/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-α antagonist in HIV-infected patients who do not benefit sufficiently from antiretroviral treatment, and in other conditions in which increased levels of TNF-α may contribute to hematopoietic deficiencies.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume26
Issue number2
DOIs
StatePublished - 1 Feb 2001
Externally publishedYes

Keywords

  • AIDS
  • BFU-E
  • GM-CFC
  • Hematopoiesis
  • TNF-binding protein 1
  • TNF-α-Soluble TNF-α receptor

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