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Naltrexone inhibits alcohol‐mediated enhancement of HIV infection of T lymphocytes
Author(s) -
Wang Xu,
Douglas Steven D.,
Peng JinSong,
Metzger David S.,
O’Brien Charles P.,
Zhang Ting,
Ho WenZhe
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1105642
Subject(s) - naltrexone , biology , human immunodeficiency virus (hiv) , alcohol , immunology , pharmacology , virology , biochemistry , receptor , antagonist
Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol‐mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env‐pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific μ‐opioid receptor antagonist, Cys 2 , Tyr 3 , Arg 5 , Pen 7 (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous β‐endorphin production and induced μ‐opioid receptor mRNA expression in PBL and CEMX174 cells. The role of β‐endorphin in alcohol‐mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol‐ or exogenous β‐endorphin‐mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV‐infected alcoholics.