In Vivo Imaging of Translocator Protein, a Marker of Activated Microglia, in Alcohol Dependence

Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [(11)C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol dependent subjects. Alcohol dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink. Linear mixed modeling of partial volume corrected [(11)C]PBR28 data revealed a main effect of alcohol dependence (p=0.034), corresponding to 10% lower TSPO levels in alcohol dependent subjects. Within this group, exploratory analyses found a negative association of TSPO levels in hippocampus and striatum with alcohol dependence severity (p<0.035). Peripheral immune response was assessed in a subset of subjects by measuring cytokine expression from monocytes cultured both in the presence and absence of lipopolysaccharide. Peripheral monocyte response to lipopolysaccharide stimulation was lower in alcohol dependent subjects compared to controls for the pro-inflammatory cytokines IL-6 and IL-8. Thus, alcohol dependent individuals exhibited less activated microglia in brain and a blunted peripheral pro-inflammatory response compared to controls. These findings suggest a role for pharmaceuticals tuning the neuroimmune system as therapeutics for alcohol dependence.