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 he matopoietic failure often observed in patients with AIDS. Soluble TNF recep tors (sTNFR) compete for TNF-alpha with cell surface receptors and thus may block its activity. The effect of the p55 sTNFR (recombinant TNF-binding p rotein-1 [rTBP-1]) on the clonogenic growth of hematopoietic progenitor cel ls from 27 HIV-infected patients was evaluated in comparison with 11 normal study subjects. Peripheral blood-derived, myelopoietic (i.e., granulomonoc ytic colony-forming cells [GM-CFC]) and erythropoietic (i.e, burst-forming unit, erythroid [BFU-E]) colonies were grown in 10-day semisolid cultures w ith increasing concentrations of rTBP-1. Significantly, dose-dependent incr eases 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 fail ed to induce any appreciably increased colony formation in normal cell cult ures. In 6 patients treated with highly active antiretroviral treatment (HA ART), TBP-1 alone did not demonstrate the in vitro hematopoiesis-enhancing effect. This study may provide an initial step in development of therapeuti c 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 def iciencies.