Role of macrophages in Staphylococcus aureus-induced arthritis and sepsis

Objective. A model of hematogenously induced Staphylococcus aureus arthriti s was used to analyze the role of macrophages in this highly destructive co ndition. In this model, the majority of cells in the cartilage-synovial jun ction that participate in the destructive process are macrophages, Methods. To assess the role of monocytes/macrophages in staphylococcal arth ritis, mice were inoculated with S aureus or given phosphate buffered salin e as control. Mice were rendered monocytopenic by administration of etoposi de, a drug that selectively depletes the monocyte/macrophage population. Results. Throughout the course of infection, the etoposide-treated mice exh ibited a significantly less severe arthritis than the control animals. Thes e data were confirmed by histopathologic analysis of the joints. The down-r egulation of development of arthritis was accompanied by decreased serum le vels of the proinflammatory cytokines tumor necrosis factor (I and interleu kin-6, In contrast, infection-triggered mortality was increased in the etop oside-treated mice as compared with the control animals. Notably, the monoc ytopenic 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 t he pathogenesis of S aureus-induced infection. On the one hand, absence of macrophages leads to a favorable outcome concerning the severity of arthrit ic lesions, but on the other hand, the clearance of bacteria by monocytes/m acrophages is decreased, resulting in poor survival.