Baseline Inflammation but Not Exercise Modality Impacts Exercise-induced Kynurenine Pathway Modulation in Persons With Multiple Sclerosis: Secondary Results From a Randomized Controlled Trial

Overview

Journal Int J Tryptophan Res

Publisher Sage Publications

Specialty Biochemistry

Date 2024 Nov 13

PMID 39534856

Authors

Marie Kupjetz

Nadine Patt

Niklas Joisten

Per Magne Ueland

Adrian McCann

Roman Gonzenbach

Jens Bansi

Philipp Zimmer

Affiliations

Soon will be listed here.

Abstract

Background: The kynurenine pathway (KP) is an important hub in neuroimmune crosstalk that is dysregulated in persons with multiple sclerosis (pwMS) and modulated by exercise in a modality-specific manner.

Objectives: To compare changes in the KP metabolite profile of pwMS (1) following combined treatments including either high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) during a 3-week multimodal rehabilitation, (2) to evaluate exercise response in relation to baseline systemic inflammation, and (3) to investigate associations of kynurenines with physical capacity and clinical outcomes.

Methods: For this secondary analysis of a randomized controlled trial, serum concentrations of kynurenines at baseline and after 3 weeks were determined using targeted metabolomics (LC-MS/MS). Exercise-induced changes in the KP metabolite profile according to treatment and baseline systemic inflammation (neutrophil-to-lymphocyte ratio (NLR) <3.12 versus ⩾3.12) were investigated using covariance analyses.

Results: Regardless of treatment, concentrations of tryptophan and most kynurenines decreased over time. Quinolinic acid concentration increased ( < .001). Participants with low and high NLR revealed differential exercise-induced changes in concentrations of kynurenines and NLR. The systemic inflammation markers neopterin ( = .015) and NLR ( < .001) decreased in the whole group and in participants with high NLR, respectively.

Conclusions: Combined treatments including HIIT or MICT do not differentially modulate the KP metabolite profile, with both reducing concentrations of most kynurenines. Baseline systemic inflammation may impact exercise-induced changes in the KP metabolite profile and anti-inflammatory effects of exercise in pwMS.

Trial Registration: clinicaltrials.gov (identifier: NCT04356248).

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