Engagement with visual art has been associated with reduced stress and improved well-being, but the biological mechanisms underlying these effects remain unclear. This study tested whether viewing paintings in a gallery elicits distinct immune and physiological responses compared with viewing matched high-quality reproductions in a laboratory. Fifty predominantly university-affiliated healthy adults (18-40 yrs) were quasi-randomly assigned to view either original paintings in a gallery (n = 25) or reproductions in a controlled laboratory environment (n = 25). Salivary cortisol and pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IL-8) were measured before and after viewing and heart rate variability (HRV) and skin temperature were recorded continuously during a 20-minute viewing session. Linear mixed-effects models adjusting for sampling interval revealed a significant Time × Group interaction for IL-6 (F(1,45.99) = 5.98, p = 0.018), reflecting a larger pre-to-post reduction in the gallery condition (∼30%) with no significant change in the laboratory group. Cortisol showed a similar interaction (F(1,45) = 8.73, p = 0.005), with a greater decrease in the gallery condition (∼22%). TNF-α decreased over time overall but showed no significant interaction, while IL-1β and IL-8 showed no significant effects. Gallery viewers exhibited more dynamic autonomic activity, including higher HRV and brief skin-temperature drops. Laboratory viewers showed a flatter HRV profile and gradual warming. Only the gallery condition showed cross-system associations: larger vagally mediated HRV responses (SDNN, HF) correlated with greater reductions in cortisol and IL-6. Viewing authentic artworks in a museum setting was associated with coordinated endocrine, inflammatory, and autonomic changes not observed when viewing reproductions in a laboratory context.
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