Experimental stress suppresses recruitment of macrophages but enhanced their P-gingivalis LPS-stimulated secretion of nitric oxide

Background: Epidemiological studies have suggested that stress can alter th e onset and progression of periodontal disease. However, the mechanisms inv olved are not clear. The present study was designed to examine whether the functional response of mouse macrophages stimulated by Porphyromonas gingiv alis lipopolysaccharide (LPS) is affected by experimental stress, and to in vestigate the role of corticosterone (CS) in the stress-related effects. Methods: Two models of stress were used: emotional (isolation) and physical (cold). We measured thioglycollate-induced macrophage recruitment in vivo, and LPS-induced nitric oxide (NO) secretion by the macrophages in vitro. T wo groups of mice were exposed to the stress conditions: isolation or cold. A third group was injected daily with CS, and a fourth group was used as a control (no stress). After 3 days of stress conditions, thioglycollate was injected into the peritoneal cavity. Four days later, peritoneal macrophag es were isolated, counted, and cultured. The secretion of NO by the culture d cells was evaluated with and without P. gingivalis LPS stimulation. Results: The number of cells in the peritoneal lavage of stressed mice was significantly reduced in comparison to macrophages isolated from non-stress ed animals. The number of macrophages from CS-treated mice did not differ f rom controls. NO secretion from unstimulated macrophages did not differ bet ween the stressed and control groups. Stimulation of the macrophages with P . gingivalis LPS significantly enhanced NO secretion by macrophages from th e control and stressed animals, but not by the CS-treated group. NO levels secreted by P. gingivalis-stimulated cells from the two stressed groups wer e significantly higher than the levels secreted by controls, and the isolat ion group released significantly higher levels than the cold group. Stimula tion of the macrophages with P. gingivalis LPS and interferon (IFN)-gamma r esulted in enhanced NO secretion in the 4 groups compared to LPS alone, wit h no significant differences between the groups. Conclusions: The results suggest that experimental stress modulates the res ponse of macrophages to inflammatory stimulants, and that CS is not the sol e mediator involved. The presence of IFN-gamma in the culture may mask the functional differences induced by stress. The stress-induced upregulation o f NO secretion might be involved in the accelerated periodontal destruction in stressed subjects.