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ORIGINAL RESEARCH ARTICLE

High Plasma Levels of MCP-1 and Eotaxin Provide Evidence for an Immunological Basis of Fibromyalgia

Zhifang Zhang^*, Gregory Cherryholmes^*, Allen Mao^*, Claudia Marek, Jeffrey Longmate, Michael Kalos, R. Paul ST. Amand and John E. Shively^*,1

^* Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010; Fibromyalgia Treatment Center, Los Angeles, California 90064; Division of Biostatistics and Bioinformatics, City of Hope, Duarte, California 91010; and Division of Cancer Immunotherapy and Tumor Immunology, City of Hope, Duarte, California 91010

To whom requests for reprints should be addressed at ¹ Division of Immunology, Beckman Research Institute of the City of Hope, 1450 E. Duarte Road, Duarte, CA 91010. E-mail: jshively{at}coh.org

Fibromyalgia (FMS), a predominantly female (85%) syndrome, affects an estimated 2% of the US population with skeletal muscle ache, fatigue, headache, and sleep disorder. The pathogenesis of FMS is unknown and there is no laboratory test for diagnosis. In this study, plasma levels of 25 cytokines and chemokines in 92 female patients with FMS and 69 family members were measured compared to 77 controls. Trans-endothelial migration of normal leukocytes in response to FMS plasma and the cytokine profile of human myoblasts were analyzed. High levels of MCP-1 (P < 0.001) and eotaxin (P < 0.01) were found in patients and family members compared to controls. Patients (56/92) treated with the single agent guaifenesin (>3 months) had higher levels of eotaxin than those not treated (P < 0.01). Diluted plasma from patients increased the migration of normal eosinophils and monocytes, but not neutrophils, through an endothelial/Matrigel barrier only when mast cells are included in the lower wells (P < 0.05). Furthermore, myoblasts can secrete MCP-1, eotaxin, and IP-10, while treatment with MCP-1 caused secretion of IL-1β, eotaxin and IP-10. FMS is associated with inflammatory chemokines, that MCP-1 and eotaxin may contribute to the symptoms of FMS, and that similar cytokine profiles found in family members support the idea that FMS has a genetic component. Furthermore, the chemokine profile associated with FMS has direct effects on the migration of eosinophils and monocytes in the presence of mast cells, and skeletal muscle itself may secrete

Key Words: fibromyalgia • chemokine • MCP-1 • eotaxin • myoblasts