An in vitro model of morphine withdrawal manifests the enhancing effect on human immunodeficiency virus infection of human T lymphocytes through the induction of substance P.
Opioid withdrawal is a crucial and recurring event during the course of opioid abuse that has a negative impact on the immune system. In this study, we investigated whether abrupt withdrawal (AW) or precipitated withdrawal (PW) potentiates human immunodeficiency virus (HIV) infection of human T lymphocytes. AW and PW enhanced HIV infection of peripheral blood lymphocytes and T-cell lines (Jurkat and CEMX174). In addition, both AW and PW induced HIV replication in a latently HIV-infected human T-cell line (J1.1). The enhancing effect of AW and PW was associated with the induction of neuropeptide substance P in both peripheral blood lymphocytes and the T-cell lines. The substance P receptor antagonist, CP-96,345, not only blocked AW- or PW-induced endogenous substance P expression but also abrogated AW- or PW-induced HIV replication in T cells. These findings provide a cellular mechanism that supports the notion that opioids have a co-factor role in promoting HIV infection of the immune cells.
Wang
Xu
X
Department of Pediatrics, Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Douglas
Steven D
SD
Peng
Jin-Song
JS
Zhou
Dun-Jin
DJ
Wan
Qi
Q
Ho
Wen-Zhe
WZ
D001713:Biphenyl Compounds / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D009020:Morphine / Q000009:adverse effects* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013373:Substance P; D009020:Morphine; C066892:CP 96345