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Arthritis Rheum. 2000 Oct;43(10):2276-82.

Role of macrophages in Staphylococcus aureus-induced arthritis and sepsis.

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1
University of Göteborg, Sweden.

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.

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