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Background This study investigated the oxidative burst function of peripheral phagocytic cells (granulocytes and monocytes) and assessed the relation between oxidative burst and periodontal status in adult individuals with Down syndrome ( DS) vs. other groups. Methods Of 55 DS individuals (18-56 years old), 74 individuals with mental retardation ( MR) and 88 medically healthy controls ( HC) participated in the study. The MR and HC groups were age, race and gender matched with the DS group. Gingival index, plaque index, probing depth, attachment level and bleeding on probing were recorded for each subject. Whole blood was collected for granulocyte/monocyte oxidative burst tests. Oxidative burst was determined by flow cytometry in terms of percentage of cells actively involved in oxidative burst, and oxidative intensity (magnitude of ROIs per cell). Results The basal oxidative burst intensity of DS granulocytes was higher than that of HC and MR granulocytes ( p = 0.05). The Escherichia coli stimulated oxidative burst intensity of DS monocytes was higher than that of HC and MR monocytes ( p = 0.05). Regression analysis controlling for age, sex, race and plaque levels showed a significant association between monocyte oxidative burst intensity and loss of periodontal attachment in DS subjects ( p < 0.01). Regression analysis also showed a significant association between granulocyte oxidative burst intensity and bleeding on probing in all subjects ( p < 0.05). Conclusions Oxidative burst activity of peripheral monocytes and granulocytes is elevated in DS affected individuals and may contribute to periodontal tissue inflammation and loss of periodontal attachment in this susceptible group. [ABSTRACT FROM AUTHOR]