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Electroconvulsive therapy (ECT) is an effective treatment of depression, but its mechanism of action still remains unknown. Some studies emphasize that epileptic seizures result in cerebral production of cytokines, including the cytokine network in association with the pathophysiology of depression. We hypothesized that depressed patients would show a dysregulated profile of peripheral cytokines before and after ECT treatment.Fifteen hospitalized subjects with major depressive disorder were recruited. Human cytokine array IV was used to determine the profile of cytokines in the serum during the course of ECT. Positive results of the cytokine assay were verified by reverse transcriptase-polymerase chain reaction. Depressive symptoms were evaluated before and after ECT series.The signal intensity of eotaxin-3 and interleukin (IL)-5 changed statistically significantly between the first ECT and 24 hours after the last ECT. Furthermore, there were significant correlations between the signal intensities of eotaxin-3, bone morphogenetic protein 6, IL-5, and transforming growth factor-β and the severity of depression. The results of Cytoray assays were confirmed partly by reverse transcriptase-polymerase chain reaction. The changes of tumor necrosis factor β in pre-post comparison of ECT and the correlation of the Montgomery-Asberg Depression Scale score with tumor necrosis factor β, IL-5, and bone morphogenetic protein 6 expression could be verified. Only the relative signal intensity of IL-16 correlated significantly with the clinically as well as electroencephalographically measurable seizure duration.Electroconvulsive therapy treatment seems to change the expression of various cytokines in relation to changes of affective states such as mood. Therefore, cytokines might play a specific role within the treatment and pathogenesis of affective disorders.