Fibromyalgia (FMS) is a chronic widespread pain (CWP) and fatigue syndrome that affects three to six million adults in the United States. Core symptoms of FMS include pain, fatigue, and mood and sleep disturbances. To date, consensus has not been reached among researchers regarding the pathogenesis of FMS nor the specific role of cytokine activation on the neuroendocrine—immune response patterns in persons with FMS. The purpose of this article is to describe and synthesize the results of research studies focused on the relationship between cytokines and FMS and among cytokines and core symptoms of FMS. There is some support in the literature for relationships among FMS symptoms and cytokines; however, there are discrepant findings related to whether proinflammatory and anti-inflammatory cytokines are elevated or reduced in persons with FMS and whether their levels correlate with the core symptoms of this disorder. Although the use of cytokine biomarkers must be considered exploratory at this time due to the lack of consistent empirical findings, biobehavioral research focused on understanding the relationship of FMS with cytokines may lead to a better understanding of this complex syndrome. This knowledge may ultimately contribute to the development of interventions for symptom management that address not only the symptom manifestation but also a biological mediator of symptoms.
Abeles, A.M., Pillinger, M.H., Solitar, B.M., & Abeles, M. ( 2007). Narrative review: The pathophysiology of fibromyalgia . Annals of Internal Medicine, 146, 726-734.
2.
Amel Kashipaz, M.R., Swinden, D., Todd, I., & Powell, R.J. ( 2003). 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, 132, 360-365.
3.
Ardiç, F., Özgen, M., Aybek, H., Rota, S., Çubukçu, D., & Gökgöz, A. (2007). Effects of balneotherapy on serum IL-1, PGE2 and LTB4 levels. Rheumatology International , 27, 441-446.
4.
Bazzichi, L., Rossi, A., Massimetti, G., Giannaccini, G., Giuliano, T., De Feo, F., et al. (2007). Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clinical and Experimental Rheumatology, 25, 225-230.
5.
Beck, A.T., Rush, A.J., Shaw, B.F., & Emery, G. ( 1979). Cognitive therapy for depression. New York: Guilford Press.
6.
Bennett, R.M. ( 2008). Fibromyalgia and chronic fatigue syndrome. In L. Goldman & D. Ausiello (Eds.), Cecil medicine (pp. 2078-2082). Philadelphia, PA: Saunders Elsevier.
7.
Carpenter, K.J. ( 2006). The mystery of fibromyalgia, part I-Is fibromyalgia real pain, and what causes it?Psychopharmacology Educational Update , 1, 2-3.
8.
Corwin, E.J. ( 2000). Understanding cytokines part I: Physiology and mechanism of action. Biological Research for Nursing, 1, 30-40.
9.
First, M.B., Spitzer, R.L., Gibbon, M., & Williams, J.B.W. (1997). Structured clinical interview for DSM-IV axis-I disorders (SCID-I). Washington, DC: American Psychiatric Press, Inc.
10.
Gür, A., Karakoc, M., Erdogan, S., Nas, K., Cevik, R., & Sarac, A.J. ( 2002a). Regional cerebral blood flow and cytokines in young females with fibromyalgia. Clinical and Experimental Rheumatology , 20, 753-760.
11.
Gür, A., Karakoc, M., Nas, K., Remzi, Cevik, Denli, A., et al. (2002b). Cytokines and depression in cases with fibromyalgia. The Journal of Rheumatology, 29, 358-361.
12.
Gustot, T., Lemmers, A., Louis, E., Nicaise, C., Quertinmont, E., Belaiche, J., et al. (2005). Profile of soluble cytokine receptors in chrohn’s disease. Gut, 54, 488-495.
13.
Hader, N., Rimon, D., Kinarty, A., & Lahat, N. ( 1991). Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis and Rheumatism, 34, 866-872.
14.
Hamilton, M. ( 1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry, 23, 56-62.
15.
Hesse-Husain, J. ( 2007). Fibromyalgia: A psychoneuroimmunological perspective [Electronic version]. Retrieved March 5, 2008, from University of Trier, Department for Theoretical and Clinical Psychobiology , http://ubt.opus.hbz-nrw.de/volltexte/2007/405/
16.
Jones, K.D., Burckhardt, C.S., Deodar, A.A., Perrin, N.A., Hanson, G.C., & Bennett, R.M. ( 2008). A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia. Arthritis & Rheumatism, 58, 612-622.
17.
Jones, K.D., Ross, R.L., Adams, D.G., & Bennett, R.M. ( 2006). Fibromyalgia: Rational management in primary care. Clinician Reviews, 16, 42-48. Retrieved March 5, 2008, from http://www. clinicianreviews.com/index.asp?show=lesson&page=courses/ 105241/lesson.htm&lsn_id=105241
18.
Katz, R.S., Wolfe, F., & Michaud, K. ( 2006). Fibromyalgia diagnosis: A comparison of clinical, survey, and American college of rheumatology criteria. Arthritis and Rheumatism, 54, 169-176.
19.
Kelley, K.W., Bluthe, R.M., Dantzer, R., Zhou, J.H., Shen, W.H., Johnson, R.W., et al. (2003). Cytokine-induced sickness behavior. Brain, Behavior, and Immunity, 17, 112-118.
20.
Kirschbaum, C., Pirke, K.M., & Hellhammer, D.H. (1993). The ‘trier social stress test’-A tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology, 28, 76-81.
21.
Lawrence, R.C., Felson, D.T., Helmick, C.G., Arnold, L.M., Choi, H., Deyo, R.A., et al. (2008). Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. part II. Arthritis and Rheumatism, 58, 26-35.
22.
Levine, S.J. ( 2004). Mechanisms of soluble cytokine receptor generation. Journal of Immunology, 173, 5343-5348.
23.
Macedo, J.A., Hesse, J., Turner, J.D., Ammerlaan, W., Gierens, A., Hellhammer, D.H., et al. (2007). Adhesion molecules and cytokine expression in fibromyalgia patients: Increased L-selectin on monocytes and neutrophils . Journal of Neuroimmunology, 188, 159-166.
24.
Maes, M., Libbrecht, I., Van Hunsel, F., Lin, A.H., De Clerck, L., Stevens, W., et al. (1999). The immune-inflammatory pathophysiology of fibromyalgia: Increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines. Psychoneuroendocrinology , 24, 371-383.
25.
Mease, P. ( 2005). Fibromyalgia syndrome: Review of clinical presentation, pathogenesis, outcome measures, and treatment. The Journal of Rheumatology Supplement, 75, 6-21.
26.
Mease, P., Arnold, L.M., Bennett, R., Boonen, A., Buskila, D., Carville, S., et al. (2007). Fibromyalgia syndrome. The Journal of Rheumatology, 34, 1415-1425.
27.
Miller, A.H. ( 2003). Cytokines and sickness behavior: Implications for cancer care and control. Brain, Behavior, and Immunity, 17, 132-134.
28.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). (2004). Questions and answers about fibromyalgia. Retrieved December 2, 2008, from http://www.niams.nih.gov/Health_Info/Fibromyalgia/default.asp
29.
Smythe, H. ( 2006). Editorial: The symptom intensity scale, fibromyalgia, and the meaning of fibromyalgia-like symptoms. A review. Journal of Rheumatology, 33, 2113-2114.
30.
Toedter, G., Hayden, K., Wagner, C., & Brodmerkel, C. (2008). Simultaneous detection of eight analytes in human serum by two commercially available platforms for multiplex cytokine analysis. Clinical and Vaccine Immunology , 15, 42-48.
31.
Üçeyler, N., Valenza, R., Stock, M., Schedel, R., Sprotte, G., & Sommer, C. ( 2006). Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis & Rheumatism, 54, 2656-2664.
32.
Wallace, D.J. ( 2006). Is there a role for cytokine based therapies in fibromyalgia . Current Pharmaceutical Design, 12, 17-22.
33.
Wallace, D.J., Bowman, R.L., Wormsley, S.B., & Peter, J.B. ( 1989). Cytokines and immune regulation in patients with fibrositis . Arthritis and Rheumatism, 32, 1334-1335.
34.
Wallace, D.J., Linker-Israeli, M., Hallegua, D., Silverman, S., Silver, D., & Weisman, M.H. ( 2001). Cytokines play an aetiopathogenetic role in fibromyalgia: A hypothesis and pilot study. Rheumatology ( Oxford, England), 40, 743-749.
35.
Wallace, D.J., Margolin, K., & Waller, P. ( 1988). Fibromyalgia and interleukin-2 therapy for malignancy . Annals of Internal Medicine, 108, 909.
36.
Webster, J.I., Tonelli, L., & Sternberg, E.M. (2002). Neuroendocrine regulation of immunity. Annual Review of Immunology, 20, 125-163.
37.
Wolfe, F. ( 2003). Editorial: Stop using the American College of Rheumatology criteria. Journal of Rheumatology, 30, 1671-1672.
38.
Wolfe, F., Smythe, H.A., Yunus, M.B., Bennett, R.M., Bombardier, C., Goldenberg, D.L., et al. (1990). The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis and Rheumatism, 33, 160-172.
39.
Zautra, A.J., Fasman, R., Parish, B.P., & Davis, M.C. ( 2007). Daily fatigue in women with osteoarthritis, rheumatoid arthritis, and fibromyalgia. Pain, 128, 128-135.
