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

Abstract

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.

Remifentanil discontinuation and subsequent intensive care unit-acquired infection: a cohort study

“…There are biological, as well as pathological, interactions between neuropeptide substance P, which is a modulator of neuroimmunoregulation, and opiates [ 38 ]. In an in vitro model, Wang and colleagues [ 39 ] investigated the relationship between morphine withdrawal and HIV infection of human T lymphocytes. They concluded that the interaction of opiates and neuropeptide substance P in human T lymphocytes was likely to a have a role in the immunopathogenesis of HIV disease among opiate abusers.…”

Opioids and HIV/HCV Infection

“…However, different state of opiate dependency included maintenance (Metzger et al 1993; Selwyn et al 1993; Sullivan et al 2008; Zaric et al 2000), tolerance (DeLeo et al 2004; Donahoe 1993; Eisenstein et al 2006; Umbricht et al 2003) and opiate withdrawal (Donahoe 2004; Feng et al 2005, 2006b; Rahim et al 2002, 2003, 2005; Wang et al 2006) has the potentially differential effects on immune function and HIV infection. Because of the complexities of variable and conditional dependence of opiate effects, a consideration should be given to opiate use conditions (maintenance, tolerance, and opiate withdrawal) and stages (acute v.s.…”

Cell‐specific actions of HIV‐Tat and morphine on opioid receptor expression in glia

“…As Tat is actively secreted by HIV‐1‐infected cells and can interact with adjacent cells (Tardieu et al, 1992; Ensoli et al, 1993; Chirmule et al, 1995; Chang et al, 1997), it has been suggested that Tat could participate in the progression of HIVD. Indeed, Tat expression is elevated in brain tissue of patients with HIV dementia (Wesselingh et al, 1993; Hofman et al, 1994; Wiley et al, 1996) and is neurotoxic in vitro and in vivo (Hayman et al, 1993; Magnuson et al, 1995; Jones et al, 1998; Turchan et al, 2003; Turchan‐Cholewo et al, 2006). Furthermore, Tat has been shown to be potently proinflammatory (Philippon et al, 1994; Chen et al, 1997; Albini et al, 1998; Bruce‐Keller et al, 2001, 2003; Pu et al, 2003), and immunocytochemical studies have localized Tat protein to microglia and astrocytes in the brains of AIDS patients (Kruman et al, 1998; Bonwetsch et al, 1999), suggesting that Tat may be an important mediator of HIV‐mediated glial inflammatory responses in the brain.…”