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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 14, 2003; DOI: 10.1124/jpet.103.056697

0022-3565/03/3073-1158-1162$20.00
JPET 307:1158-1162, 2003
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INFLAMMATION AND IMMUNOPHARMACOLOGY

Methylnaltrexone Antagonizes Opioid-Mediated Enhancement of HIV Infection of Human Blood Mononuclear Phagocytes

Wen-Zhe Ho1, Chang-Jiang Guo1, Chun-Su Yuan, Steven D. Douglas, and Jonathan Moss

Division of Immunologic and Infectious Diseases, Joseph Stokes Jr. Research Institute of the Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (W.-Z.H., C.-J.G., S.D.D.); and Department of Anesthesia and Critical Care, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois (C.-S.Y., J.M.)

Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. We and others have recently demonstrated that opioid enhances HIV infection of human macrophages through modulation of {beta}-chemokines and the CCR5 receptor and that this effect is reversed by naltrexone, a tertiary opioid antagonist. Tertiary opioid antagonists cannot be used in opioid-dependent patients because they precipitate withdrawal or reversal of analgesia. We determined whether the quaternary opioid antagonist methylnaltrexone (MNTX), now in phase III clinical trials for opioid-induced constipation, reverses the opioid-mediated enhancement of HIV infection of macrophages at clinically relevant doses. MNTX completely abrogated morphine-induced HIV Bal strain infection of macrophages. MNTX also inhibited the R5 strain (ADA) envelope-pseudotyped HIV replication induced by morphine. Furthermore, MNTX abolished morphine-mediated up-regulation of CCR5 receptor expression. The ability of MNTX to block opioid-induced CCR5 expression and HIV replication at clinically relevant doses may have additional benefit for opioid abusers with HIV infection, or patients with AIDS pain receiving opioids.

Received July 7, 2003; accepted September 8, 2003.

Address correspondence to: Dr. Jonathan Moss, Anesthesia and Critical Care, The University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637. E-mail: jm47{at}airway.uchicago.edu




This article has been cited by other articles:


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J. Moss and C. E. Rosow
Development of Peripheral Opioid Antagonists: New Insights Into Opioid Effects
Mayo Clin. Proc., October 1, 2008; 83(10): 1116 - 1130.
[Abstract] [Full Text] [PDF]


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