Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells.
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 in 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 pentoxifylline treatment because of its blockage of TNF-alpha-mediated HIV-1 upregulation, from increased efficacy of AZT, and also from improvement in TNF-alpha-induced cachexia.
Fazely
F
F
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Beth Israel Hospital, Boston, MA 02115.
Dezube
B J
BJ
Allen-Ryan
J
J
Pardee
A B
AB
Ruprecht
R M
RM
D000199:Actins / Q000235:genetics; D000998:Antiviral Agents; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010431:Pentoxifylline / Q000494:pharmacology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
D000199:Actins; D000998:Antiviral Agents; D015345:Oligonucleotide Probes; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D010431:Pentoxifylline