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

IF 4.1 Q3 NEUROSCIENCES International Journal of Tryptophan Research Pub Date : 2024-11-11 eCollection Date: 2024-01-01 DOI:10.1177/11786469241284423

Marie Kupjetz, Nadine Patt, Niklas Joisten, Per Magne Ueland, Adrian McCann, Roman Gonzenbach, Jens Bansi, Philipp Zimmer

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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 (p < .001). Participants with low and high NLR revealed differential exercise-induced changes in concentrations of kynurenines and NLR. The systemic inflammation markers neopterin (p = .015) and NLR (p < .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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基线炎症而非运动方式会影响多发性硬化症患者运动诱导的犬尿氨酸通路调节：随机对照试验的次要结果。

背景：犬尿氨酸通路（Kynurenine pathway，KP）是神经免疫串扰的一个重要枢纽，多发性硬化症患者（pwMS）的KP通路失调，并以特定方式受到运动的调节：目的：比较多发性硬化症患者（pwMS）（1）在为期3周的多模式康复过程中接受高强度间歇训练（HIIT）或中等强度持续训练（MICT）等综合治疗后KP代谢物谱的变化；（2）评估运动反应与基线系统炎症的关系；（3）研究犬尿氨酸与体能和临床结果的关系：在这项随机对照试验的二次分析中，采用靶向代谢组学（LC-MS/MS）测定了基线和 3 周后的犬尿氨酸血清浓度。根据治疗方法和基线全身炎症（中性粒细胞与淋巴细胞比值（NLR）），运动诱导的 KP 代谢物谱的变化结果：无论治疗与否，色氨酸和大多数犬尿氨酸的浓度都会随着时间的推移而降低。喹啉酸浓度升高（p p = .015），NLR（p 结论：HIIT、TCT 和 NLR 的综合治疗均能减轻中性粒细胞和淋巴细胞的炎症反应：包括 HIIT 或 MICT 在内的综合疗法不会对 KP 代谢物谱产生不同程度的影响，两者都会降低大多数犬尿氨酸的浓度。基线系统性炎症可能会影响运动诱导的 KP 代谢物谱变化以及运动对 pwMS 的抗炎作用。试验注册：clinicaltrials.gov（标识符：NCT04356248）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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