In Vitro Effects of Recombinant TNF-[alpha] Binding Protein (rTBP-1) on Hematopoiesis of HIV-Infected Patients.

Gradstein, Serge; Hahn, Talia; Barak, Yigal; Malach, Leah; Revel, Michel; Bentwich, Zvi; Handzel, Zeev T.
JAIDS Journal of Acquired Immune Deficiency Syndromes:
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Summary: 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 bloodderived, 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 1[mu]/ml to 25 [mu]/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.

(C) 2001 Lippincott Williams & Wilkins, Inc.