In situ hybridization analysis of synovial and systemic cytokine messenger RNA expression in superantigen-mediated Staphylococcus aureus arthritis

Abstract

Objective. To investigate patterns of synovial and systemic cytokine messenger RNA (mRNA) expression in mice with superantigen-mediated Staphylococcus aureus arthritis. Methods. Mice were inoculated intravenously with 1 x 107 colony-forming units of toxic shock syndrome toxin-1-producing S aureus LS-1. Synovial tissues and spleens were obtained at varying time intervals after bacterial inoculation, and examined for mRNA expression of interleukin-1β (IL-1β), IL-4, IL-10, IL-12, tumor necrosis factor α (TNFα), TNFβ, interferon-γ (IFNγ), transforming growth factor β, and perforin, by an in situ hybridization technique. Results. In situ hybridization revealed early synovial up-regulation of TNFα and IL-1β mRNA expression. Peak frequencies of these proinflammatory cytokines were observed at the second and third week of the infection. Expression of T cell-derived cytokine mRNAs was detected later, and in a relatively low frequency. Notably, induction and peak numbers of Th2 cytokine (IL-4 and IL-10) mRNA expression preceded Th1 cytokine (IFNγ and TNFβ) mRNAs. In comparison with synovial tissues, peak spleen cytokine mRNA expression of IL-1β, TNFα, TNFβ, IL-12, and IFNγ occurred earlier, but displayed a clearly lower magnitude of expression. Conclusion. These findings demonstrate synovial and systemic up-regulation of cytokine mRNA expression during S aureus arthritis, indicating that both monocyte/macrophage and T cell-derived products are involved in the pathogenesis of this disease.