The effects of exercise on complement system proteins in humans: a systematic scoping review

Area of Science:

• Immunology
• Exercise Physiology

Background:

• The complement system comprises classical, lectin, and alternative pathways crucial for immune responses.
• Complement-dependent cytotoxicity (CDC) is a key mechanism for monoclonal antibody therapies.
• The impact of exercise on human complement proteins remains largely uncharacterized.

Purpose of the Study:

• To systematically review the association between exercise and soluble complement proteins in healthy humans.
• To investigate effects of acute exercise, exercise training, and habitual physical activity on complement system proteins.

Main Methods:

• A systematic literature search identified 77 eligible studies with 10,236 participants.
• Studies examined associations between blood complement proteins and acute exercise, training interventions, or physical activity.
• Included 40 different complement proteins and their fragments.

Main Results:

• Higher exercise training and cardiorespiratory fitness correlated with reduced blood C3.
• Muscle strength showed a negative association with C1q levels.
• Acute exercise elevated anaphylatoxins (C3a-des-Arg, C4a-des-Arg, C5a), while ultra-endurance and resistance training increased various complement pathway markers for up to 72 hours.

Conclusions:

• Acute exercise increases anaphylatoxins, whereas longer-duration or muscle-damaging exercise elevates complement proteins for up to 72 hours.
• Exercise training generally reduces C3 and is linked to improved cardiorespiratory fitness.
• Exercise modulates complement proteins, with potential implications for CDC-dependent therapies requiring further investigation.