Systematic review with meta-analysis: cytokines in fibromyalgia syndrome

Nurcan Uçeyler, Winfried Häuser, Claudia Sommer, Nurcan Uçeyler, Winfried Häuser, Claudia Sommer

Abstract

Background: To perform a systematic review and meta-analysis on cytokine levels in patients with fibromyalgia syndrome (FMS).

Methods: Through December 2010 we systematically reviewed the databases PubMed, MEDLINE, and PsycINFO and screened the reference lists of 22 review articles for suitable original articles. Original articles investigating cytokines in patients with FMS were included. Data were extracted by two independent authors. Differences of the cytokine levels of FMS patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed applying methodological scores: modified Center of Evidence Based Medicine, Newcastle-Ottawa-Scale, and Würzburg Methodological Quality Score.

Results: Twenty-five articles were included investigating 1255 FMS patients and 800 healthy controls. Data of 13/25 studies entered meta-analysis. The overall methodological quality of studies was low. The results of the majority of studies were not comparable because methods, investigated material, and investigated target cytokines differed. Systematic review of the selected 25 articles revealed that FMS patients had higher serum levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8, and higher plasma levels of IL-8. Meta-analysis of eligible studies showed that FMS patients had higher plasma IL-6 levels compared to controls (SMD = -0.34 [-0.64, -0.03] 95% CI; p = 0.03). The majority of investigated cytokines were not different between patients and controls.

Conclusions: The pathophysiological role of cytokines in FMS is still unclear. Studies of higher quality and with higher numbers of subjects are needed.

Figures

Figure 1
Figure 1
Algorithm of study selection. The Figure displays the details of the study search and selection process.

References

    1. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P. et al.The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis and rheumatism. 1990;33:160–172. doi: 10.1002/art.1780330203.
    1. Häuser W, Zimmer C, Felde E, Kollner V. [What are the key symptoms of fibromyalgia? Results of a survey of the German Fibromyalgia Association] Schmerz (Berlin, Germany) 2008;22:176–183.
    1. Branco JC, Bannwarth B, Failde I, Abello Carbonell J, Blotman F, Spaeth M, Saraiva F, Nacci F, Thomas E, Caubere JP. et al.Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum. 2010;39:448–453. doi: 10.1016/j.semarthrit.2008.12.003.
    1. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG. et al.Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis and rheumatism. 2008;58:26–35. doi: 10.1002/art.23176.
    1. Üçeyler N, Sommer C. Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett. 2008;437:194–198. doi: 10.1016/j.neulet.2008.03.050.
    1. Menzies V, Lyon DE. Integrated review of the association of cytokines with fibromyalgia and fibromyalgia core symptoms. Biol Res Nurs. 2010;11:387–394. doi: 10.1177/1099800409348328.
    1. Gür A, Oktayoğlu P. Status of immune mediators in fibromyalgia. Current pain and headache reports. 2008;12:175–181. doi: 10.1007/s11916-008-0031-4.
    1. Bernardy K, Klose P, Üçeyler N, Kopp I, Hauser W. [Methodological fundamentals for the development of the guideline.] Schmerz (Berlin, Germany) 2008.
    1. Centre. TNC. 5.0 for Windows edn. Copenhagen: The Cochrane Collaboration; 2010. Review Manager (RevMan)
    1. Amel Kashipaz MR, Swinden D, Todd I, Powell RJ. Normal production of inflammatory cytokines in chronic fatigue and fibromyalgia syndromes determined by intracellular cytokine staining in short-term cultured blood mononuclear cells. Clinical and experimental immunology. 2003;132:360–365. doi: 10.1046/j.1365-2249.2003.02149.x.
    1. Ardıç F, Özgen M, Aybek H, Rota S, Çubukçu D, Gökgöz A. Effects of balneotherapy on serum IL-1, PGE2 and LTB4 levels in fibromyalgia patients. Rheumatology international. 2007;27:441–446. doi: 10.1007/s00296-006-0237-x.
    1. Barth H, Berg PA, Klein R. Is there any relationship between eosinophilia myalgia syndrome (EMS) and fibromyalgia syndrome (FMS)? An analysis of clinical and immunological data. Advances in experimental medicine and biology. 1999;467:487–496. doi: 10.1007/978-1-4615-4709-9_61.
    1. Bazzichi L, Giacomelli C, De Feo F, Giuliano T, Rossi A, Doveri M, Tani C, Wilson RB, Bombardieri S. Antipolymer antibody in Italian fibromyalgic patients. Arthritis research & therapy. 2007;9:R86. doi: 10.1186/ar2285.
    1. Bazzichi L, Rossi A, Massimetti G, Giannaccini G, Giuliano T, De Feo F, Ciapparelli A, Dell'Osso L, Bombardieri S. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clinical and experimental rheumatology. 2007;25:225–230.
    1. Blanco I, Beritze N, Arguelles M, Carcaba V, Fernandez F, Janciauskiene S, Oikonomopoulou K, de Serres FJ, Fernandez-Bustillo E, Hollenberg MD. Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients. Clinical rheumatology. 2010;29:1403–1412. doi: 10.1007/s10067-010-1474-7.
    1. Blanco I, Janciauskiene S, Nita I, Fernandez-Bustillo E, Carcaba V, Gallo C, Alvarez-Rico M, de Serres F, Beridze N. Low plasma levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFalpha), and vascular endothelial growth factor (VEGF) in patients with alpha1-antitrypsin deficiency-related fibromyalgia. Clinical rheumatology. 2010;29:189–197. doi: 10.1007/s10067-009-1318-5.
    1. Feng J, Zhang Z, Li W, Shen X, Song W, Yang C, Chang F, Longmate J, Marek C, St Amand RP. et al.Missense mutations in the MEFV gene are associated with fibromyalgia syndrome and correlate with elevated IL-1beta plasma levels. PloS one. 2009;4:e8480. doi: 10.1371/journal.pone.0008480.
    1. Hader N, Rimon D, Kinarty A, Lahat N. Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis and rheumatism. 1991;34:866–872. doi: 10.1002/art.1780340712.
    1. Hernandez ME, Becerril E, Perez M, Leff P, Anton B, Estrada S, Estrada I, Sarasa M, Serrano E, Pavon L. Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index. BMC research notes. 2010;3:156. doi: 10.1186/1756-0500-3-156.
    1. Iannuccelli C, Di Franco M, Alessandri C, Guzzo MP, Croia C, Di Sabato F, Foti M, Valesini G. Pathophysiology of fibromyalgia: a comparison with the tension-type headache, a localized pain syndrome. Annals of the New York Academy of Sciences. 2010;1193:78–83. doi: 10.1111/j.1749-6632.2009.05365.x.
    1. Kaufmann I, Eisner C, Richter P, Huge V, Beyer A, Chouker A, Schelling G, Thiel M. Lymphocyte subsets and the role of TH1/TH2 balance in stressed chronic pain patients. Neuroimmunomodulation. 2007;14:272–280. doi: 10.1159/000115041.
    1. Macedo JA, Hesse J, Turner JD, Ammerlaan W, Gierens A, Hellhammer DH, Muller CP. Adhesion molecules and cytokine expression in fibromyalgia patients: increased L-selectin on monocytes and neutrophils. Journal of neuroimmunology. 2007;188:159–166. doi: 10.1016/j.jneuroim.2007.06.002.
    1. Maes M, Libbrecht I, Van Hunsel F, Lin AH, De Clerck L, Stevens W, Kenis G, de Jongh R, Bosmans E, Neels H. The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines. Psychoneuroendocrinology. 1999;24:371–383. doi: 10.1016/S0306-4530(98)00087-0.
    1. Ortega E, Bote ME, Giraldo E, Garcia JJ. Aquatic exercise improves the monocyte pro- and anti-inflammatory cytokine production balance in fibromyalgia patients. Scandinavian journal of medicine & science in sports. 2010.
    1. Pay S, Çalgüneri M, Çalışkaner Z, Dinç A, Apras S, Ertenli I, Kiraz S, Çobankara V. Evaluation of vascular injury with proinflammatory cytokines, thrombomodulin and fibronectin in patients with primary fibromyalgia. Nagoya journal of medical science. 2000;63:115–122.
    1. Ross RL, Jones KD, Bennett RM, Ward RL, Druker BJ, Wood LJ. Preliminary Evidence of Increased Pain and Elevated Cytokines in Fibromyalgia Patients with Defective Growth Hormone Response to Exercise. The open immunology journal. 2010;3:9–18.
    1. Salemi S, Rethage J, Wollina U, Michel BA, Gay RE, Gay S, Sprott H. Detection of interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in skin of patients with fibromyalgia. The Journal of rheumatology. 2003;30:146–150.
    1. Schwarz MJ, Offenbaecher M, Neumeister A, Ewert T, Willeit M, Praschak-Rieder N, Zach J, Zacherl M, Lossau K, Weisser R. et al.Evidence for an altered tryptophan metabolism in fibromyalgia. Neurobiology of disease. 2002;11:434–442. doi: 10.1006/nbdi.2002.0563.
    1. Togo F, Natelson BH, Adler GK, Ottenweller JE, Goldenberg DL, Struzik ZR, Yamamoto Y. Plasma cytokine fluctuations over time in healthy controls and patients with fibromyalgia. Experimental biology and medicine (Maywood, NJ. 2009;234:232–240. doi: 10.3181/0808-RM-254.
    1. Üçeyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C. Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. 2006;54:2656–2664. doi: 10.1002/art.22026.
    1. Wallace DJ, Linker-Israeli M, Hallegua D, Silverman S, Silver D, Weisman MH. Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology (Oxford, England) 2001;40:743–749. doi: 10.1093/rheumatology/40.7.743.
    1. Wang H, Moser M, Schiltenwolf M, Buchner M. Circulating cytokine levels compared to pain in patients with fibromyalgia -- a prospective longitudinal study over 6 months. The Journal of rheumatology. 2008;35:1366–1370.
    1. Zhang Z, Cherryholmes G, Mao A, Marek C, Longmate J, Kalos M, Amand RP, Shively JE. High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia. Experimental biology and medicine (Maywood, NJ) 2008;233:1171–1180. doi: 10.3181/0712-RM-328.
    1. Gür A, Karakoç M, Nas K, Remzi, Çevik, Denli A, Saraç J. Cytokines and depression in cases with fibromyalgia. The Journal of rheumatology. 2002;29:358–361.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel