Do Inflammatory Cytokines Mediate the Therapeutic Benefits of Exercise in Depressive Disorders? A Scoping Review of Recent English Literature

Abstract

Introduction: Studies have investigated the pathogenesis of depression, with few focusing on the elevation of pro-inflammatory cytokine levels in depression. This article undertakes a scoping review of the available research to explore the current understanding of the role of pro-inflammatory cytokines in depression. Furthermore, the ability of exercise to reduce depression severity through lowering these cytokine levels is examined. Method: Analysis of online research articles was used to investigate the intended objective, and 18 English-based papers published between 2010-2020 were selected. These studies examined pro-inflammatory cytokine levels in healthy, depressed, diseased and/or physically active patients or research animals as a primary or secondary outcome. Other inclusion criteria such as number of participants and appropriate control selection were used to further refine the search results. Results: Based on the conducted search, sufficient evidence seems to exist to support an association between elevated levels of pro-inflammatory cytokines, IL-6, TNF-α, IL-1β and incidence of depression. Exercise increases the production and release of anti-inflammatory cytokines and reduces baseline levels of pro-inflammatory cytokines. These anti-inflammatory properties of physical activity supported by exercise-focused studies, can explain the mechanism behind reduced depressive symptoms after a period of regular exercise. Discussion: The available data supports an association between elevated pro-inflammatory cytokine levels and depression, and the antidepressant effects of exercise. However, there is no evidence of causality between elevated levels of pro-inflammatory cytokines and depression. Whether pro-inflammatory cytokine levels changed as a result of regular exercise, the specific types of pro-inflammatory cytokines that experienced the change, and the extent to which they did, depended on the participant, and the exercise activity. Conclusion: Measuring the levels of pro-inflammatory cytokines can potentially provide an objective method for diagnosing depression. Due to the potential anti-inflammatory effects of exercise, programs can be designed as a non-pharmacological treatment in mild cases and augment the effectiveness of drug therapy in severe cases.