Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells
Fazely, F.; Dezube, B.J.; Allen-Ryan, J.; Pardee, A.B.; Ruprecht, R.M.
Blood 77(8): 1653-1656
ISSN/ISBN: 0006-4971 PMID: 1707692 DOI: 10.1182/blood.v77.8.1653.1653
Pentoxifylline (Trental) used routinely for the treatment of intermittent claudication, has been shown previously to decrease the levels of tumor necrosis factors-.alpha. (TNF-.alpha.) RNA in cancer patients and to lead to a general improvement of well being. Increased TNF-.alpha. levels have been observed not only in cancer patients but also in cachectic patients with the acquired immunodeficiency syndrome (AIDS), and TNF-.alpha. is known to increase the expression of the human immunodeficiency virus type 1 (HIV-1) via activating its long terminal repeat (LTR). Moreover, TNF-.alpha. decreases the therapeutic efficacy of zidovudine (AZT). Here we show a significant decrease in HIV-1 replication by pentoxifylline is infected human peripheral blood mononuclear cells. The reduction was proportional to the downregulation of expression of a reporter gene, the bacterial gene for chloramphenicol acetyl transferase, linked to the HIV-1 LTR in human monocytoid cells. We conclude that patients with AIDS may benefit from pentoxyifylline treatment because of its blockage of TNF-.alpha.-mediated HIV-1 upregulation, from increased efficacy of AZT, and also form improvement in TNF-.alpha.-induced cachexia.