Abstract
Substantial evidence supports the view that inflammatory processes contribute to brain alterations in HIV infection. Mechanisms recently proposed to underlie neuropathology in Alcohol Use Disorder (AUD) include elevations in peripheral cytokines that sensitize the brain to the damaging effects of alcohol. This study included 4 groups: healthy controls, individuals with AUD (abstinent from alcohol at examination), those infected with HIV, and those comorbid for HIV and AUD. The aim was to determine whether inflammatory cytokines are elevated in AUD as they are in HIV infection. Cytokines showing group differences included interferon gamma-induced protein 10 (IP-10) and tumor necrosis factor α (TNFα). Follow-up t-tests revealed that TNFα and IP-10 were higher in AUD than controls but only in AUD patients who were seropositive for Hepatitis C virus (HCV). Specificity of TNFα and IP-10 elevations to HCV infection status was provided by correlations between cytokine levels and HCV viral load and indices of liver integrity including albumin/globulin ratio, fibrosis scores, and AST/platelet count ratio. Because TNFα levels were mediated by HCV infection, this study provides no evidence for elevations in peripheral cytokines in "uncomplicated", abstinent alcoholics, independent of liver disease or HCV infection. Nonetheless, these results corroborate evidence for elevations in IP-10 and TNFα in HIV and for IP-10 levels in HIV+HCV co-infection.
Highlights
Patients with chronic HIV infection typically show elevations in plasma cytokine levels [1,2,3,4]
Additional 7-group ANOVAs demonstrated that the albumin/globulin ratio (AGR: F (204) = 11.45, p < .0001; Fig 3B) was low and FIB-4 (F(204) = 11.78, p < .0001; Fig 3C) and AST/platelet count ratio (APRI) (F(204) = 8.56, p < .0001; Fig 3D) scores were high in the Hepatitis C virus (HCV)-infected subgroups
Our results show that elevations in peripheral cytokines are associated not with an Alcohol Use Disorder (AUD) diagnosis, but were associated with co-occurring HCV infection in abstinent drinkers
Summary
Patients with chronic HIV infection typically show elevations in plasma cytokine levels [1,2,3,4]. Activation of macrophages and microglia and the release of chemokines, cytokines, and neurotoxins [19] promote further HIV replication [20], trafficking of macrophages into the CNS [21], glial activation [22], altered neuronal signaling and repair processes [23,24,25,26], and compromised neuronal integrity [27,28,29,30,31]. Select studies in HIV patients have reported correlations between.
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