Increased plasma endothelin-1 levels in fibromyalgia syndrome

M. Pache, J. Ochs1, E. Genth1, R. Mierau1, T. Kube2 and J. Flammer

University Eye Clinic, Basel, Switzerland
1 Research Institute of Rheumatic Diseases, Rheumaklinik Aachen, Germany and
2 University Eye Clinic, Freiburg, Germany

SIR, The fibromyalgia syndrome (FMS) is defined by symptoms of widespread, chronic musculoskeletal pain, stiffness and pressure hyperalgesia at characteristic soft tissue sites, called soft tissue tender points. FMS shows clinical overlap with other stress-associated disorders, including chronic fatigue syndrome (CFS) and depression. The disease is more common in women than in men, and occurs mostly in middle age. Despite intensive research in this field, the aetiology of the disorder is still elusive. Autoimmune mechanisms as well as a genetic predisposition have been discussed [1, 2]. Disturbances in the serotoninergic system, the pain processing systems and the stress axis were identified but also questioned [3, 4]. Moreover, a tendency towards cold extremities and cold-induced vasospasm has been demonstrated in some FMS patients [5, 6].

The peptide endothelin-1 (ET-1), mainly produced by epithelial cells, is one of the most potent physiological vasoconstrictors known so far. Increased plasma levels of ET-1 could explain some of the above-mentioned symptoms of vascular dysregulation occurring in patients with FMS. Elevated ET-1 plasma levels have already been demonstrated in various other rheumatological diseases, such as rheumatoid arthritis, giant cell arteritis and lupus erythematosus [7]. Therefore, in this study, we evaluated whether plasma ET-1 levels of patients with FMS differ from those of healthy controls. Twenty-one patients (M:F=2:19; mean age: 46±8 yr, range: 31–60 yr) who fulfilled the criteria of the American College of Rheumatology (ACR) for FMS were recruited by J.O. and E.G. A detailed medical history was taken, and all subjects completed a systemic examination. Exclusion criteria were major systemic diseases (e.g. chronic heart failure, renal failure, glomerulonephritis, major arterial hypertension, autoimmune diseases other than FMS) and a history of drug or alcohol abuse. The healthy controls (M:F=2:19; mean age: 46±8 yr, range: 32–63 yr) consisted of companions of our patients, and of hospital staff not involved in research. All participants gave written informed consent for all procedures. The protocol was approved by the Ethical Committee of the University of Aachen, Germany, and followed the tenets of the Helsinki declaration. Venous EDTA blood samples (20 ml) were taken after 30 min of rest in a supine position at room temperature. The blood samples were stored immediately on ice and cool centrifugation at 4°C was performed in due course. ET-1 plasma levels were determined by specific radioimmunoassay as previously described [8]. Statistical analyses were performed using the paired t-test and Spearman rank correlation. P values of less than 0.05 were considered statistically significant. Values are given in mean±standard deviation.

A comparison of the plasma ET-1 levels of FMS patients and controls is presented in Fig. 1Go. Plasma ET-1 levels were significantly increased in FMS patients when compared with controls (2.74±0.76 pg/ml, range 1.68–3.95 vs 1.4±0.23 pg/ml, range 0.9–1.86; P<0.0001). No correlation between ET-1 and age, body mass index, disease duration or number of tender points was found. Increased production of ET-1 has already been described in a variety of other vascular and autoimmune diseases [7]. It is, however, still unclear whether the elevated ET-1 plasma levels contribute to the multifactorial aetiology, or whether they are merely an epiphenomenon of these diseases. ET-1 is mainly synthesized by vascular endothelial cells, which are known to modulate local vascular tone by releasing relaxing factors such as nitric oxide or constrictive factors such as ET-1. Apart from its direct vasoconstrictive effect, ET-1 also increases the sensitivity of blood vessels to the action of other vasoconstrictive circulating hormones such as noradrenaline, serotonin and angiotensin II. In some vascular beds such as the heart [9] and kidney [10], an increased production of ET-1 after tissue ischaemia has been demonstrated. As mentioned above, FMS patients frequently show a distinctive vascular cold-response [5, 6]. It is therefore conceivable that a repeated relative ischaemia due to a vascular dysregulation might increase the ET-1 levels in FMS patients. An elevated ET-1 level in turn might further enhance vasospasm, thereby creating a vicious circle. However, further studies to clarify the relationship between the elevated plasma ET-1 and the above-mentioned symptoms of vascular dysregulation in FMS are required to draw firm conclusions.



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FIG. 1. The plasma levels of ET-1 in patients with FMS compared with healthy controls.

 

Notes

Correspondence to: J. Flammer, University Eye Clinic Basel, Mittlere Str. 91, PO Box, CH-4012 Basel, Switzerland. E-mail: josef.flammer{at}uhbs.ch Back

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Accepted 16 September 2002