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Fibromyalgia (FM) is thought to occur because of the combination of interactions among neurotransmitters, such as neuropeptide Y (NPY), stressors, hormones, cytokines, and both the immune and sympathetic nervous systems. The aim of this study was to evaluate serum concentrations of cytokines, antipolymer antibodies (APA), and NPY in 51 patients with FM, 25 with tension-type headache (TTH), and 15 healthy controls. Serum concentrations of eight different cytokines, APA and NPY, were measured. Interleukin (IL)-1RA, IL-6, IL-10, and tumor necrosis factor-alpha were higher in serum of FM patients compared with TTH patients and a significant correlation between IL-10 and Fibromyalgia Impact Questionnaire score was observed. There was a significant difference between FM and TTH versus controls in NPY levels, but not in APA levels. Cytokines and NPY take part in pain modulation and even if they are altered in FM they cannot be considered as measurable biomarkers of disease.