Drug abuse, innate immunity and hepatitis C virus

Abstract

Since its discovery in 1989, hepatitis C virus (HCV) has become a major public health problem. HCV chronically infects an estimated 170 million people worldwide. The seroprevalence of anti-HCV antibody in the United States has been estimated at 1.8%, which corresponds to approximately 4 million people. HCV is the most common chronic blood borne infection in the United States, and the leading cause of liver transplantation in developed countries. Injection drug use is the dominant mode of HCV transmission and accounts for up to 90% of current infections. Opiates and other drug abuse, such as alcohol, have been implicated as cofactors in the pathogenesis of HCV disease. Injection drug use has been the most common risk factor identified in alcoholics with HCV infection. Both opiates and alcohol contribute significantly to morbidity and mortality from HCV disease. These drugs most likely act synergistically to promote the development and progression of HCV disease. However, there is limited information available concerning the interaction of the drug abuse with the host cell innate immunity against HCV infection, which is a major barrier to fundamental understanding of the immunopathogenesis of HCV disease. Therefore, defining the role of the drug abuse in the development of chronic HCV infection is of crucial importance and should provide practical guidance toward the reduction of risk factors that interfere with therapeutic approaches for HCV infection and disease. This review paper focuses on the interplay between drug abuse (opiates and alcohol), innate immunity and HCV in the context of the development of HCV disease.

Increased plasmacytoid dendritic cell maturation and natural killer cell activation in HIV-1 exposed, uninfected intravenous drug users

“…Our observations are of interest in light of the controversial role of opioids on NK cell function where contrasting data suggests that opioids can inhibit NK activity or can lead to a “tolerant” state that is dependent on frequency of drug use and timing of NK analysis relative to drug exposure [40–42]. Based upon the frequency and duration of injection drug use among the EU-IDU subjects in our cohort (see table 1), we speculate that the innate immune response of EU-IDU subjects reaches an equilibrium state after years of prolonged injection-drug use.…”

Opioids and HIV/HCV Infection

“…Although the role of opiates in promoting HIV disease is still debatable, overwhelming evidence indicates that heroin and other opiate-derived substances affect both innate and adaptive immunity (Donahoe and Vlahov 1998; McCarthy et al 2001; Wang et al 2008b; Zhang et al 2006). Opiate abusers have higher incidence of infectious diseases, which may be directly related to impaired immune functions (Alonzo and Bayer 2002; Nair et al 1997; Novick et al 1989; Ochshorn et al 1990; Peterson et al 1993; Wang et al 2008b).…”

Morphine Suppresses IFN Signaling Pathway and Enhances AIDS Virus Infection

“…Although the role of opiates in promoting HIV disease progression is still debatable, overwhelming evidence indicates that heroin and other opiate derived substances affect both adaptive and innate immunity [20], [21], [22], [23]. Innate immunity is the first line of the defense mechanism against viral infections.…”