Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis

O’Mahony, Luke Furtado; Srivastava, Arnav; Mehta, Puja; Ciurtin, Coziana

doi:10.1093/rheumatology/keab146

Cited by 65 publications

(58 citation statements)

References 51 publications

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“…The presence of a common pathway mediated by immune dysregulation provides a common cause of these conditions, and IL-6 is elevated in these syndromes. 52 , 53 , 54 , 55 , 56 Interleukin 6 is associated with fatigue and sleep disturbance in chronic stress and inflammation in CS syndromes. 57 Diagnosis of these conditions has traditionally been frustrating as patients will have multiple disabling symptoms yet will have few (if any) abnormalities on laboratory and procedural testing.…”

Section: Discussionmentioning

confidence: 99%

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

Ganesh

Grach

Ghosh

et al. 2022

Mayo Clinic Proceedings

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Objective To describe the clinical data from the first 108 patients seen in the Mayo Clinic post–COVID-19 care clinic (PCOCC). Methods After Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review. Results Most of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P =.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively. Conclusion In our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

Ganesh

Grach

Ghosh

et al. 2022

Mayo Clinic Proceedings

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“…The presence of a common pathway mediated by immune dysregulation provides a common etiology of these conditions and IL-6 is elevated in these syndromes. [51][52][53][54][55] IL-6 is associated with fatigue and sleep-disturbance in chronic stress and inflammation in central sensitization syndromes. 56 Treatment of these conditions have traditionally been frustrating as patients will have multiple disabling symptoms yet will have very few (if any) abnormalities on laboratory and procedural testing.…”

Section: Discussionmentioning

confidence: 99%

The Female Predominant Persistent Immune Dysregulation of the Post COVID Syndrome: A Cohort Study

Ganesh

Grach

Bierle

et al. 2021

Preprint

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Objective: To describe the clinical data from the first 107 patients seen in the Mayo Clinic Post COVID-19 Care Clinic (PCOCC). Patients and Methods: After IRB approval, we reviewed the charts of 107 patients seen between January 19, 2021 and April 29, 2021 in the Mayo Clinic Post COVID Care Clinic (PCOCC) in order to describe the first 107 patients treated through the Mayo Clinic PCOCC. Data was abstracted from the electronic medical record into a standardized database to facilitate analysis. Phenotypes of patients seen in the PCOCC clinic were identified by expert review of predominant symptom clusters. Results: The majority of patients seen in our clinic were female (75%, 80/107), and the median age at presentation was 47 years (interquartile range [IQR] 37, 55). All had Post Acute Sequelae of SARS-CoV-2 infection (PASC) with six clinical phenotypes being identified: fatigue predominant (n=68), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women (84%, p=0.006) and the dyspnea-predominant phenotype was more common in men (52%, p=0.002). IL-6 was elevated in 61% of patients (69% of women, p=0.0046) which was statistically discordant with elevation in CRP and ESR which was identified in 17% and 20% of cases respectively (p<0.001). Four PASC phenotypes (fatigue-predominant, myalgia-predominant, orthostasis predominant, and headache-predominant) were associated with central sensitization (CS), and higher IL-6 levels than those phenotypes not associated with CS (p=0.013). Patients with CS phenotypes after COVID-19 infection (post COVID syndrome) were predominantly female (80%, p=0.0085). Conclusion: In our post COVID clinic, we observed several distinct clinical phenotypes. Fatigue-predominance was the most common presentation and was associated with elevated IL-6 levels and female gender. Dyspnea-predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were significantly elevated in patients with PASC and discordant with ESR and CRP, particularly in those with central sensitization phenotypes.

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“…All these previous works demonstrated that MAO-A inhibition was able to decrease ROS generation and the ROS-activated inflammatory process in particular through NF-κB pathway inhibition. Several studies showed that inflammatory cytokines in fibromyalgia patients could drive disturbances in neural networks during the interaction of the nervous system with immune cells, which eventually could lead to an increase in central and peripheral sensitization as well as neuroinflammation [23]. For all these reasons, the aim of this study was to investigate the therapeutic potential of metaxalone in an in vitro experimental paradigm of microglial cell inflammation (obtained through IL-1β stimulation) [24] that mimics the phenomenon of neuroinflammation involved in several neurological disorders, including fibromyalgia.…”

Section: Introductionmentioning

confidence: 99%

MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells

Pallio

D’Ascola

Cardia

et al. 2021

IJMS

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Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1β (IL-1β). Control cells and IL-1β-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 µM) for six hours. IL-1β stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPARγ), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression. IL-1β also augmented MAO-A expression/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation.

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Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis

Cited by 65 publications

References 51 publications

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

The Female Predominant Persistent Immune Dysregulation of the Post COVID Syndrome: A Cohort Study

MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells

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