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First published online June 5, 2008
Proceedings of the Society for Experimental Biology and Medicine doi: 10.3181/0712-RM-328
© 2008 by the Society for Experimental Biology and Medicine

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Regular Manuscript

High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia

Zhifang Zhang 1, Gregory Cherryholmes 1, Allen Mao 1, Claudia Marek 2, Jeffrey Longmate 1, Michael Kalos 1, R. Paul St. Amand 2, and John E Shively 1*

1 City of Hope
2 Fibromyalgia Treatment Center

* To whom correspondence should be addressed. E-mail: jshively{at}coh.org.


   Abstract

Fibromylagia (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. Transendothelial migration of normal leukocytes in response to FMS plasma and the cytokine profile of human skeletal muscle cells 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, skeletal muscle cells can secrete MCP-1, eotaxin, and IP-10, while treatment with MCP-1 caused secretion of IL-1{beta}, 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 cytokines associated with FMS.

Key Words: fibromyalgia, MCP-1, eotaxin, chemokine, skeletal muscle







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Copyright © 2008 by the Society for Experimental Biology and Medicine.