Baseline Inflammation but not Exercise Modality Impacts Exercise-induced Kynurenine Pathway Modulation in Persons...

Area of Science:

• Neuroimmunology
• Metabolomics
• Exercise Physiology

Background:

• The kynurenine pathway (KP) is crucial in neuroimmune interactions and is altered in multiple sclerosis.
• Exercise can modulate the KP, but its effects may differ based on exercise intensity.

Purpose of the Study:

• To compare KP metabolite changes in multiple sclerosis patients after HIIT versus MICT during rehabilitation.
• To assess if baseline inflammation affects exercise response and KP modulation.
• To explore links between kynurenines, physical capacity, and clinical outcomes.

Main Methods:

• Secondary analysis of a randomized controlled trial involving 3-week multimodal rehabilitation with HIIT or MICT.
• Targeted metabolomics (LC-MS/MS) measured serum kynurenine concentrations at baseline and post-intervention.
• Covariance analyses examined exercise-induced changes in KP metabolites, considering treatment and baseline neutrophil-to-lymphocyte ratio (NLR).

Main Results:

• Tryptophan and most kynurenines decreased, while quinolinic acid increased, irrespective of exercise type.
• Participants with high baseline NLR showed different exercise-induced changes in kynurenines and NLR.
• Systemic inflammation markers (neopterin, NLR) decreased, particularly in those with high baseline NLR.

Conclusions:

• Combined HIIT and MICT similarly modulated the KP metabolite profile, generally decreasing kynurenine levels.
• Baseline systemic inflammation appears to influence exercise-induced KP alterations and the anti-inflammatory effects of exercise in multiple sclerosis patients.