Methamphetamine enhances Hepatitis C virus replication in human hepatocytes

Abstract

Very little is known about the interactions between hepatitis C virus (HCV) and methamphetamine, which is a highly abused psychostimulant and a known risk factor for human immunodeficiency virus (HIV)/HCV infection. This study examined whether methamphetamine has the ability to inhibit innate immunity in the host cells, facilitating HCV replication in human hepatocytes. Methamphetamine inhibited intracellular interferon alpha expression in human hepatocytes, which was associated with the increase in HCV replication. In addition, methamphetamine also compromised the anti-HCV effect of recombinant interferon alpha. Further investigation of mechanism(s) responsible for the methamphetamine action revealed that methamphetamine was able to inhibit the expression of the signal transducer and activator of transcription 1, a key modulator in interferon-mediated immune and biological responses. Methamphetamine also down-regulated the expression of interferon regulatory factor-5, a crucial transcriptional factor that activates the interferon pathway. These in vitro findings that methamphetamine compromises interferon alpha-mediated innate immunity against HCV infection indicate that methamphetamine may have a cofactor role in the immunopathogenesis of HCV disease.

Methamphetamine administration modifies leukocyte proliferation and cytokine production in murine tissues

“…One of the mechanisms by which METH can cause exacerbation of HCV infection is, in part, linked to a reduced number of macrophages and a mixed Th1-Th2 phenotype immune response, which is what we observed in the METH-treated animals in this study. Thus, METH might play a role in facilitating HCV replication in human hepatocytes (Ye, Peng et al 2008). Our findings provide fundamental insights into how METH may play an important role in HCV infection-related morbidity and mortality.…”

Neuroimmune Basis of Methamphetamine Toxicity

“…A growing literature demonstrates that methamphetamine exposure and activation of microglia and astrocytes (as well as other cell types) alters peripheral and central immune functions (In, Son, Rhee, & Pyo, 2005; In et al, 2004; Liang et al, 2008; Martinez et al, 2009; Ye et al, 2008) and that immune factors such as cytokines (e.g., IL-1β, IL-6, and TNF-α), chemokines [e.g., monocyte chemotactic protein-1 (MCP-1)], and adhesion molecules play a critical role in the development and persistence of methamphetamine-induced neuronal injury and neuropsychiatric impairments (Clark et al, 2013; Loftis et al, 2011; Yamamoto, Moszczynska, & Gudelsky, 2010; Yamamoto & Raudensky, 2008). In an astrocytic cell line, methamphetamine exposure for 3 days increases IL-6 and IL-8 RNA levels by 4.6 ± 0.2 fold and 3.5 ± 0.2 fold, respectively (Shah et al, 2012).…”

Substance use disorders: Psychoneuroimmunological mechanisms and new targets for therapy

“…Besides addiction, substance abuse and dependence are linked to a variety of medical disorders, including increased prevalence of infectious diseases [ e.g ., HIV/AIDS (Kresina et al, 2004) and hepatitis C viral infection (HCV) (Klevens et al, 2012)], cancer, heart and liver disease, and others. The increased prevalence of medical disorders has been attributed, in part, to altered immune function in patients with a history of substance abuse (Arria et al, 1991; Liang et al, 2008; Loftis et al, 2006; Ye et al, 2008). …”