Paradoxical relationships of interleukin-6 and tumor necrosis factor-alpha with methamphetamine use and body mass index

Abstract Background: Methamphetamine (MA) use and obesity are linked to inflammation and related comorbidities, yet their combined effects are poorly understood. We evaluated associations between MA use, body mass index (BMI), and systemic inflammation. Methods: We analyzed data and specimens from 140 men in a longitudinal cohort with biannual visits, over 4 visits (560 specimens). We created a three-level MA use variable by combining urine drug tests with past 6-month self-reported MA use: no use, intermittent use, and frequent use. Serum samples were analyzed for interleukin (IL)−6 and tumor necrosis factor (TNF)-α. Mixed-effects linear models assessed associations between MA use and cytokine levels. Interaction terms evaluated the joint effect of MA and BMI on inflammation. Results: Median age is 35. Across visits, MA use is frequent (19.3% of visits), intermittent (19.1%), and none (61.6%). BMI is lowest among those with frequent MA use ( p < 0.001). MA use and BMI are positively associated with IL-6, but their interaction is negatively associated with both IL-6 and TNF-α. Conclusions: MA use and BMI appear to jointly influence systemic inflammation. Frequent MA use combined with higher BMI is associated with lower IL-6 and TNF-α, potentially reflecting reduced energy expenditure and increased appetite contributing to higher BMI.