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


CONCLUSIONS
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.
Verdrengh
M
M
University of Göteborg, Sweden.
Tarkowski
A
A
D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D007970:Leukopenia / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide