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Local inhibition of endogenous IL-18 through adenoviral overexpression of IL-18BPc results in reduced incidence and severity of collagen induced arthritis in mice

  • RL Smeets
  • AAJ van de Loo
  • LAB Joosten
  • AJ Arntz
  • MB Bennink
  • WB van den Berg
Meeting abstract
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Keywords

Collagen Induce Arthritis Acquire Immunity Joint Cavity Experimental Arthritis Induce Arthritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

IL-18 is a member of the interleukin-1 family and plays an important role in innate and acquired immunity. Previous experiments focused on IL-18 in experimental arthritis showed that neutralization through systemic treatment with either antibodies or IL-18 binding protein (IL-18BP) ameliorated the disease. To study the local role of IL-18 in arthritis we developed a replication deficient adenoviral vector containing the murine IL-18BP isoform c gene (Ad5CMV.IL-18BPc). The neutralizing ability of adenoviral overexpressed IL-18BPc on IL-18 response was tested in vitro. Supernatants of IL-18BP transfected cells significantly inhibited IL-18 induced luciferase production in IL-18 sensitive NFkB luciferase reporter fibroblasts. Next we injected 1 × 107PFU of Ad5CMV.IL-18BPc or the control vector Ad5CMV.Luc into the murine knee joint cavity of DBA/1 mice before onset of collagen-induced arthritis (CIA). IL-18BPc overexpression significantly reduced local knee joint swelling in CIA with 66% (P < 0.001) and distal paw swelling with approx. 50% (P < 0.01) compared to the control vector. Furthermore, local IL-18BPc resulted in lower serum levels of IL-6 compared to the control (respectively 5.0 pg/ml and 12.7 pg/ml, P < 0.001). Serum titers of specific IgG1, IgG2a and total IgG antibodies directed towards collagen type II showed no significant differences between control and IL-18BPc treatment, indicating that the effect seen on arthritis by overexpression of IL-18BPc in the joint was not caused by an IL-18BPc effect on humoral immunity. These results clearly show that IL-18 present in the arthritic joint plays an important proinflammatory role and demonstrate that adenoviral overexpression of IL-18BPc in the synovium is an efficacious local treatment in experimental arthritis.

Copyright information

© BioMed Central Ltd 2002

Authors and Affiliations

  • RL Smeets
    • 1
  • AAJ van de Loo
    • 1
  • LAB Joosten
    • 1
  • AJ Arntz
    • 1
  • MB Bennink
    • 1
  • WB van den Berg
    • 1
  1. 1.UMC NijmegenNijmegenThe Netherlands

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