In Vitro Effects of Recombinant TNF-?? Binding Protein (rTBP-1) on Hematopoiesis of HIV-Infected Patients

Abstract

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.