Does the relationship between health and behavior depend on changes in immune functioning?

BACKGROUND: Psychoneuroimmunology research has explored how stress and health behaviors may influence disease risk through immune mechanisms, often relying on surrogate biomarkers such as cytokines, cortisol, and natural killer cell activity to explain health outcomes. PURPOSE: This narrative review critically evaluates whether behavioral and psychological interventions improve health outcomes by modifying immune function. METHODS: Evidence from systematic reviews, landmark reports, and conceptual frameworks published over the past eight decades is reviewed, assessing the degree to which immune markers serve as effective mediators of behavioral health benefits. RESULTS: While stress and social adversity are consistently associated with certain immune parameters, randomized trials have not shown that modifying these markers reliably improves patient-centered outcomes (e.g. quality of life, functioning, or longevity). Behavioral interventions appear to benefit health primarily through pathways other than immune modulation. CONCLUSIONS: These findings suggest that behavioral medicine should shift its focus to outcomes meaningful to patients, rather than surrogate immunologic markers. Future work should prioritize functional capacity, health-related quality of life, and life expectancy as primary endpoints.