Utilizing blood inflammatory markers in alcohol studies: Considerations and recommendations for study design, sample collection, and data analysis

A large body of evidence suggests that heavy alcohol use is associated with dysregulated immune function, and that immune dysfunction in turn contributes to the pathophysiology of alcohol use disorder (AUD). As such, alcohol researchers have increasingly begun to include measurements of immune function—primarily peripheral circulating cytokines—in human studies, with the goal of testing associations with clinically-relevant behavioral measures. To date, findings and implications from these studies have been inconsistent and difficult to interpret, likely due to methodological challenges related to study design and implementation. In particular, the existing literature has demonstrated sample processing concerns, differences in assay methods, limited selection of analytes, and sample selection biases, all of which may contribute to inconsistent results. We briefly review the field, discuss these and other challenges, and propose guidance for designing studies on inflammation among heavy-drinking human participants. We note that conducting such studies requires appreciable consideration and planning, and ideally should involve an interdisciplinary team of experts, including immunologists, physiologists, and technical experts in bioassays, alongside experts in the field of interest (e.g., AUD). We highlight the importance of considering participant selection, analyte selection, sample collection, sample handling and storage, and assay methods, and suggest that the field move towards standardization of procedures and reporting. We propose that undertaking these changes in study design and implementation should produce consilience in findings and aid in our overall understanding of the complex relationship between alcohol exposure and immune function.