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Widespread Pain and Serum IL-8 Levels in Fibromyalgia Patients

widespread pain fibromyalgia
Widespread Pain – IL-8 Levels – Fibromyalgia

Ozdolap S, et al. recently reported, at the European League against Rheumatism (EULAR) Annual European Congress of Rheumatology, June 10-13, 2015, a positive correlation between widespread pain and serum IL-8 in patients with fibromyalgia (FM).

Fibromyalgia is characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues, and women are more likely to develop fibromyalgia than are men. FM patients are highly sensitive to painful and innocuous stimuli, including touch, heat, cold, chemicals, light, sound, and smell.

Currently, the diagnosis of fibromyalgia is reached after eliminating the possibility of rheumatic and psychiatric diseases, which represents a 2 or 3 year period before a specific diagnosis can be made.

Although heightened pain sensitivity is a hallmark of FM, little is known about the factors (genetic and otherwise) that contribute to the development of this disease. Recent evidence indicates that cytokines and especially chemokines contribute to the pathogenesis of FM.

Cytokines, depending on their concentration, induce symptoms, such as fatigue, fever, sleep, pain, and myalgia, all of which develop in FM patients. Until recently, no infectious or degenerative event that was responsible for the variation in these levels had been identified in FM patients, although factors, such as obesity, can cause these alterations.

Alterations in proinflammatory cytokine levels have been observed in the serum and biopsies of FM patients. Maria E Hernandez et al., showed that FM patients had different circulatory levels of IL-6 and TNF-α. In addition, increased levels of IL-1Ra and IL-6 have been found in the supernatants of cells from FM patients in vitro stimulation and cellular proliferation studies. IL-6 increased significantly but TNF-α levels decreased in these FM patients.

Other reports have noted an association of high levels of IL-6 with painful events, surgical procedures and certain psychiatric disorders, as well as between fatigue and pain in animal models.

In the Ozdolap S, et al. study reported, at the EULAR Annual 2015 Congress forty-eight patients with fibromyalgia who met the American College of Rheumatology (ACR) 2010 criteria and 43 healthy women were enrolled. Widespread pain was evaluated using a Visual analog scale (VAS), the Widespread Pain Index (WPI) and the Symptom Severity Scale (SSS), and blood sera were analyzed for tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1-beta, IL-8 and oxidized low-density lipoprotein (LDL).

Although no overall differences in TNF-alpha, IL-1-beta, IL-8 and oxidized LDL were seen between the groups, a relationship with VAS and serum IL-8 and TNF-a were observed in the patient group.

The work of Ozdolap S, et al. substantiates previous work indicating that the pro-inflammatory chemokine IL-8 may contribute to the pathogenesis of fibromyalgia (Wang H. et al., 2009). In this study, before and during the inpatient therapy, the serum level of IL-8 was significantly higher in patients with FM compared with controls but did not correlated with pain intensity and medication.

Of note, higher cerebrospinal fluid (CSF) levels of IL-8 in FM patients were also recently reported (Kadetoff D. et al., 2012; Kosek E. et al., 2015). Interestingly, exercise interventions might exert an anti-inflammatory effect, as exercise appear to reduce serum IL-8 and IL-6 levels.

IL-8, also known as neutrophil chemotactic factor is a chemokine known to activate neutrophils and is an important factor for the migration and infiltration of neutrophils at inflammation sites.

An Update

A 2017 study published in the Journal of Pain Research reports the presence of high levels of the chemokines CX3CL1 (also known as fractalkine) and interleukin-8 in fibromyalgia patients.

In this study, Emmanuel Bäckryd and colleagues from the Pain and Rehabilitation Center, Linköping University, Sweden investigated the CSF and plasma inflammatory profiles of FM patients.

The investigators applied the multiplex proximity extension assay. They found elevated IL-8 levels in both CSF and plasma FM samples, whereas high levels of CX3CL1 were monitored only in CSF samples.

In 2018, the groupd of Şenay ÖZDOLAP  published in Archives of Rheumatology a full research article, entitled: ‘Pro-inflammatory Cytokines and Oxidized Low-Density-Lipoprotein in Patients With Fibromyalgia’. In this article Funda Canpolat KUTU, Şenay ÖZDOLAP, and Selda SARIKAYA report that there was no difference in levels of the serum TNF-α, IL-1β, IL-8, and Ox-LDL between FM patients and healthy controls.

But the severity of pain was significantly associated with IL-8 and TNF-α levels, and Ox-LDL level was found to be related to symptom severity of FM.

Other pro-inflammatory cytokines, such as interleukin (IL)-17A might also be involved in the development of FM.

The role of IL-8, in general, as a mediator of pain was first suggested by F.Q. Cunha et al. back in 1991.

Read More: healio.com/rheumatology


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