Fatigue in Inflammatory Rheumatic Disorders: Pathophysiological Mechanisms

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2019 Nov 5

PMID 31682277

Citations 21

Authors

S Mechiel Korte

Rainer H Straub

Affiliations

Soon will be listed here.

Abstract

Today, inflammatory rheumatic disorders are effectively treated, but many patients still suffer from residual fatigue. This work presents pathophysiological mechanisms of fatigue. First, cytokines can interfere with neurotransmitter release at the preterminal ending. Second, a long-term increase in serum concentrations of proinflammatory cytokines increase the uptake and breakdown of monoamines (serotonin, noradrenaline and dopamine). Third, chronic inflammation can also decrease monoaminergic neurotransmission via oxidative stress (oxidation of tetrahydrobiopterin [BH4]). Fourth, proinflammatory cytokines increase the level of enzyme indoleamine-2, 3-dioxygenase activity and shunt tryptophan away from the serotonin pathway. Fifth, oxidative stress stimulates astrocytes to inhibit excitatory amino acid transporters. Sixth, astrocytes produce kynurenic acid that acts as an antagonist on the α7-nicotinic acetylcholine receptor to inhibit dopamine release. Jointly, these actions result in increased glutamatergic and decreased monoaminergic neurotransmission. The above-described pathophysiological mechanisms negatively affect brain functioning in areas that are involved in fatigue.

Citing Articles

Patient-Reported Fatigue Associated with Joint Histopathology in Rheumatoid Arthritis.

Pearce-Fisher D, Smith M, Mehta B, Spolaore E, DiCarlo E, Sun D ACR Open Rheumatol. 2025; 7(1):e11772.

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Fatigue patterns surrounding biologic disease-modifying antirheumatic drug injection in patients with an inflammatory rheumatic disease: an ecological momentary assessment study.

van Lint J, Vriezekolk J, Jessurun N, den Broeder A, van den Bemt B, Huiskes V Rheumatol Int. 2025; 45(1):24.

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Association between Proinflammatory Cytokines and Anxiety and Depression Symptoms in Rheumatoid Arthritis Patients: A Cross-sectional Study.

Parlindungan F, Hidayat R, Ariane A, Shatri H Clin Pract Epidemiol Ment Health. 2023; 19:e174501792304261.

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Potential Mechanism of Fatigue Induction and Its Management by JAK Inhibitors in Inflammatory Rheumatic Diseases.

Felis-Giemza A, Massalska M, Roszkowski L, Romanowska-Prochnicka K, Ciechomska M J Inflamm Res. 2023; 16:3949-3965.

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Fatigue in Inflammatory Joint Diseases.

Chmielewski G, Majewski M, Kuna J, Mikiewicz M, Krajewska-Wlodarczyk M Int J Mol Sci. 2023; 24(15).

PMID: 37569413 PMC: 10418999. DOI: 10.3390/ijms241512040.

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