# Circulating Cytokines Mediate the Protective Effect of Physical Activity on Cardiovascular Diseases: A Mendelian Randomization Mediation Analysis

## TL;DR

This study finds that physical activity reduces heart disease risk partly by affecting immune system proteins like IL10RB.

## Contribution

The study identifies IL10RB as a novel mediator linking physical activity to reduced ischemic heart disease risk.

## Key findings

- Physical activity is inversely associated with ischemic heart disease risk.
- IL10RB mediates about 6.65% of the protective effect of physical activity on ischemic heart disease.
- Cytokine networks, particularly IL10RB signaling, may explain part of the cardiovascular benefits of exercise.

## Abstract

Cardiovascular diseases (CVDs) represent a major public health concern globally, being one of the leading causes of illness and death across populations. While physical activity is widely recognized as a protective factor against these diseases, the exact biological mechanisms that explain this relationship are still not fully understood. This study utilized a two-sample Mendelian randomization (MR) method to investigate the potential role of circulating cytokines in mediating the effects of physical activity on major CVD outcomes, including coronary artery disease (CAD), heart failure (HF), and ischemic heart disease (IHD). Our primary MR analysis revealed an inverse association between physical activity and IHD risk. Moreover, a two-step MR mediation approach identified IL10RB (Interleukin-10 receptor subunit beta) as an intermediate mediator, explaining about 6.65% of the observed contribution of physical activity to IHD. These results indicate that physical activity may mitigate CVD risk through modulation of immune pathways, particularly via IL10RB signaling. Our findings underscore the significance of cytokine networks in mediating the cardiovascular benefits of exercise and suggest potential therapeutic strategies for CVD risk reduction through immune system modulation.