Imaging the brain's immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography

Abstract

In humans, the negative effects of alcohol are linked to immune dysfunction in both the periphery and the brain. Yet acute effects of alcohol on the neuroimmune system and its relationships with peripheral immune function are not fully understood. To address this gap, immune response to an alcohol challenge was measured with positron emission tomography (PET) using the radiotracer [¹¹C]PBR28, which targets the 18-kDa translocator protein, a marker sensitive to immune challenges. Participants (n = 12; 5 F; 25-45 years) who reported consuming binge levels of alcohol (>3 drinks for females; >4 drinks for males) 1-3 months before scan day were enrolled. Imaging featured a baseline [¹¹C]PBR28 scan followed by an oral laboratory alcohol challenge over 90 min. An hour later, a second [¹¹C]PBR28 scan was acquired. Dynamic PET data were acquired for at least 90 min with arterial blood sampling to measure the metabolite-corrected input function. [¹¹C]PBR28 volume of distributions (V_T) was estimated in the brain using multilinear analysis 1. Subjective effects, blood alcohol levels (BAL), and plasma cytokines were measured during the paradigm. Full completion of the alcohol challenge and data acquisition occurred for n = 8 (2 F) participants. Mean peak BAL was 101 ± 15 mg/dL. Alcohol significantly increased brain [¹¹C]PBR28 V_T (n = 8; F_(1,49) = 34.72, p > 0.0001; Cohen's d'=0.8-1.7) throughout brain by 9-16%. Alcohol significantly altered plasma cytokines TNF-α (F_(2,22) = 17.49, p < 0.0001), IL-6 (F_(2,22) = 18.00, p > 0.0001), and MCP-1 (F_(2,22) = 7.02, p = 0.004). Exploratory analyses identified a negative association between the subjective degree of alcohol intoxication and changes in [¹¹C]PBR28 V_T. These findings provide, to our knowledge, the first in vivo human evidence for an acute brain immune response to alcohol.