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 lo7 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-lp (IL-lp), IL-4, IL-10, IL-12, tumor necrosis factor a (TNFa), TNFP, interferon-y (IFNy), transforming growth factor P, and perforin, by an in situ hybridization technique. Results. In situ hybridization revealed early synovial up-regulation of TNFa and IL-lj3 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 Thl cytokine (IFNy and TNFP) mRNAs. In comparison with synovial tissues, peak spleen cytokine mRNA expression of IL

Potential Role of Fibroblast-Like Synoviocytes in Joint Damage Induced by Brucella abortus Infection through Production and Induction of Matrix Metalloproteinases

“…Moreover, the upregulation of proinflammatory mediators in response to HKBA or L-Omp19 was accompanied by the appearance of a mixed inflammatory infiltrate in the synovium. The local upregulation of proinflammatory cytokines and MMPs agrees with previous findings in mouse models of septic arthritis by staphylococci, streptococci, and Borrelia burgdorferi (7,50,58) and also agrees with our own findings for a human case of brucellar septic bursitis (52).…”

“…The preponderant role of TNF-␣ as an MMP inducer in FLS agrees with the findings of several previous studies (12,32,33,53). It has been shown that TNF-␣ is upregulated in the joints of mice with S. aureus arthritis and that the local secretion of TNF-␣ in the joint cavity gives rise to an increased severity of arthritis (58). The second potential contribution of phagocytes to joint damage is through their secretion of MMPs upon activation by microbial molecules during phagocytosis or in response to stimulation with proinflammatory factors.…”

“…There is a rapid influx of polymorphonuclear leukocytes (PMN), later followed by the migration of mononuclear phagocytes (48). An increased expression or secretion of proinflammatory cytokines can be detected in the synovial membrane or the synovial fluid during infection in animal models and clinical cases of septic arthritis (21,38,58). Under most circumstances, the inflammatory response contains the invading pathogen and resolves the infection.…”

Inhibition of nitric oxide synthase (NOS) aggravates Staphylococcus aureus septicaemia and septic arthritis

“…IFN-g is a Th1 cytokine of importance in the pathogenesis of septic arthritis [7]. The serum levels of this cytokine were, however, essentially unaltered in the L-NMMA-treated group compared with controls (882 Ϯ 146 mU/ml versus 609 Ϯ 314 mU/ ml) in infected animals.…”

“…Macrophages play an important role in the process of joint destruction. For example, macrophage-derived cytokines such as IL-1b and tumour necrosis factor-alpha (TNF-a), found during S. aureus infection in the joint tissue [7], contribute to bone and cartilage degradation [8]. In contrast, polymorphonuclear cells are important in the defence mechanism during S. aureus infection ( [9] and Verdrengh, unpublished results).…”