Document 0851 DOCN M9620851 TI Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific cytotoxic T lymphocytes by pentoxifylline. DT 9602 AU Heinkelein M; Schneider-Schaulies J; Walker BD; Jassoy C; Institute for Virology and Immunobiology, Wurzburg University,; Germany. SO J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 1;10(4):417-24. Unique Identifier : AIDSLINE MED/96074274 AB HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the host immune response against HIV infection, and these cells release a variety of cytokines when they meet their target antigen. Since the phosphodiesterase inhibitor pentoxifylline is being used as a therapeutic agent in clinical trials of HIV infection due to its inhibitory effect on virus replication in vitro, we examined the effect of pentoxifylline on cytotoxicity and cytokine secretion by HIV-specific CD8+ CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppressed interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor release by these cells at the transcription level. Suppression of cytokine release resulted in reduced capacity of the CTLs to induce HLA class I and ICAM-1 expression and to stimulate HIV-1 replication. These results suggest that inhibition of HIV-specific CD8+ CTLs by pentoxifylline may be therapeutically relevant. Moreover, this study extends previous observations by demonstrating that, in addition to its ability to suppress cytokine production by macrophages and CD4+ T helper cells, pentoxifylline may inhibit cytotoxicity and cytokine secretion by antigen-specific CD8+ cytotoxic T lymphocytes. DE Amino Acid Sequence Blotting, Northern Cell Line Cytokines/*BIOSYNTHESIS Cytotoxicity, Immunologic/*DRUG EFFECTS CD8-Positive T-Lymphocytes/DRUG EFFECTS/METABOLISM/*VIROLOGY Flow Cytometry Gene Products, gag/CHEMISTRY Histocompatibility Antigens Class I/BIOSYNTHESIS Human HIV Antigens/CHEMISTRY HIV-1/*PHYSIOLOGY Intercellular Adhesion Molecule-1/BIOSYNTHESIS Molecular Sequence Data Pentoxifylline/*PHARMACOLOGY Phosphodiesterase Inhibitors/*PHARMACOLOGY RNA-Directed DNA Polymerase/CHEMISTRY RNA, Messenger/BIOSYNTHESIS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic/DRUG EFFECTS/METABOLISM/*VIROLOGY Virus Replication JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).