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.