Inflammatory/Stress Feedback Dysregulation in Women with Fibromyalgia

Abstract

Objective: Although one of the current hypotheses of the aetiology of fibromyalgia (FM) syndrome involves inflammatory and neuroendocrine disorders, its biophysiology still remains unclear. The purpose of the present investigation was to study the systemic inflammatory and stress responses, as well as the innate response mediated by monocytes and neutrophils in FM patients. Methods: Twenty-five women diagnosed with primary FM and 20 age-matched healthy women (control group) were enrolled in the study. Circulating ‘neuroendocrine-stress’ biomarkers (CRH, ACTH, cortisol, NA, eHsp72, serotonin and IGF-1) were evaluated by ELISA. Serum IL-8 and CRP concentrations were also determined by ELISA, and inflammatory cytokine release by monocytes [IL-1β, TNFα, IL-6, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1) and RANTES] was evaluated by the Luminex BioPlex system. The phagocytic process of neutrophils (chemotaxis, phagocytosis and microbicide capacity) was also evaluated. Results: FM patients showed an inflammatory state accompanied by an altered stress response. This is mainly manifested by high circulating levels of IL-8 and CRP (in 100% of the FM group), high circulating levels of cortisol, and increased systemic levels of NA and eHsp72. There is also increased release of inflammatory cytokines (IL-1β, TNFα, IL-6, IL-10, IL-18 and MCP-1) by monocytes, and enhanced activation of the functional capacity of neutrophils (chemotactic, phagocytic and fungicidal activities). Conclusion: An inflammatory/stress feedback dysregulation underlies FM. Whether dysregulation of the stress response is the cause of the inflammatory dysregulation or vice versa is also discussed.

Depression, sexuality and fibromyalgia syndrome: clinical findings and correlation to hematological parameters

“…It is known that cytokines such as IL-1β, TNF-α and IL-6 can trigger the inflammatory activity of FM 3,19 , and hormonal/neuronal mechanisms are probably behind this. Inflammatory mediators and cytokines can act in bone marrow and increase the production of blood cells, resulting in high hematocrit and blood hemoglobin, as observed in this study 20,21 . As well, they act in hepatocytes, altering CRP, rheumatoid factor, and complement concentrations 21,22,23 .…”

“…Inflammatory mediators and cytokines can act in bone marrow and increase the production of blood cells, resulting in high hematocrit and blood hemoglobin, as observed in this study 20,21 . As well, they act in hepatocytes, altering CRP, rheumatoid factor, and complement concentrations 21,22,23 . The pain intensity was high in patients who had a high concentration of ACTH and C3 and low concentration of immunoglobulins, which suggests a cellular immune process mediated by T cells.…”

“…The pain intensity was high in patients who had a high concentration of ACTH and C3 and low concentration of immunoglobulins, which suggests a cellular immune process mediated by T cells. These are cytokine releasers that are found to be activated in FM 3,19,20,21,22,23 . The role of hormones in FM has been investigated, and the decline of sexual hormones in the climacteric syndrome could even be a potential etiology for FM 17 .…”

“…ACTH and cortisol levels are linked to stress, pain and depression 20 , and were altered in this sample. This could indicate an imbalance of feedback mechanisms of stress and inflammation 16,19,20,21,22 , although the activation or suppression of the hypothalamus-pituitary-adrenal axis in FM remains controversial 23,24 . Besides the activation of the hypothalamus-pituitary-adrenal axis, there are low concentrations of dehydroepiandrosterone in FM patients 25 …”

Soluble fractalkine in the plasma of fibromyalgia patients

“…There is still no specific analytical diagnostic criterion for this pathology. Among the posited aetiologies of FM, special attention has been paid to the hypothesis of the involvement of inflammatory cytokines (Van West and Maes 2001), especially IL-8 (CXCL8) (Ortega et al 2009, Bote et al 2012.…”