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.

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.

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 α 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.

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.