| Abstrakt: |
To assess the role of interleukin‐18 (IL‐18) in the evolution of septic arthritis induced by group B streptococci (GBS) in mice.CD1 mice were inoculated intravenously with 8 × 106 colony‐forming units (CFU) of type IV GBS (strain 1/82), and administered intraperitoneally 1 hour before infection with anti–IL‐18 monoclonal antibodies (0.25 mg/mouse). In a subsequent set of experiments, mice infected with a suboptimal arthritogenic dose of GBS (4 × 106 CFU/mouse) were administered different doses of recombinant IL‐18 for 4 days, starting 1 hour after infection. Mortality, evolution of arthritis, bacterial clearance, joint histopathology, and cytokine production were examined in infected mice that did or did not receive treatment with anti–IL‐18 antibodies or IL‐18.IL‐18 was produced during GBS infection. Neutralization of IL‐18 resulted in a decrease in mortality rates, and in the incidence and severity of arthritis. Amelioration of arthritis was accompanied by a dramatic reduction in local IL‐1β, IL‐6, macrophage inflammatory protein 1α (MIP‐1α) and MIP‐2 production, and reduced bacterial burden. Administration of exogenous IL‐18 resulted in increased mortality rates and increased incidence and severity of GBS arthritis, concomitant with a higher number of GBS and increased levels of IL‐6, IL‐1β, MIP‐1β, and MIP‐2 production in the joints.The present study indicated some involvement of IL‐18 in the pathogenesis of GBS‐induced arthritis. The role of IL‐18 in joint pathology is shown by a regulatory effect on inflammatory mediator levels and local cell influx. Thus, IL‐18 should be regarded as a potential therapeutic target in GBS infection and arthritis. [ABSTRACT FROM AUTHOR] |
Plný text