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Title: Role of macrophages in Staphylococcus aureus-induced arthritis and sepsis. Author: Verdrengh M, Tarkowski A. Journal: Arthritis Rheum; 2000 Oct; 43(10):2276-82. PubMed ID: 11037887. Abstract: OBJECTIVE: A model of hematogenously induced Staphylococcus aureus arthritis was used to analyze the role of macrophages in this highly destructive condition. In this model, the majority of cells in the cartilage-synovial junction that participate in the destructive process are macrophages. METHODS: To assess the role of monocytes/macrophages in staphylococcal arthritis, mice were inoculated with S aureus or given phosphate buffered saline as control. Mice were rendered monocytopenic by administration of etoposide, a drug that selectively depletes the monocyte/macrophage population. RESULTS: Throughout the course of infection, the etoposide-treated mice exhibited a significantly less severe arthritis than the control animals. These data were confirmed by histopathologic analysis of the joints. The down-regulation of development of arthritis was accompanied by decreased serum levels of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-6. In contrast, infection-triggered mortality was increased in the etoposide-treated mice as compared with the control animals. Notably, the monocytopenic mice exhibited elevated bacterial burden in the blood and kidneys on days 3 and 7 after inoculation with staphylococci. CONCLUSION: This study indicates a dual role of mononuclear phagocytes in the pathogenesis of S aureus-induced infection. On the one hand, absence of macrophages leads to a favorable outcome concerning the severity of arthritic lesions, but on the other hand, the clearance of bacteria by monocytes/macrophages is decreased, resulting in poor survival.[Abstract] [Full Text] [Related] [New Search]