Cytokines in experimental autoimmune vasculitis: Evidence for a Th2 type response

Objective: To investigate the pathogenic role of cytokines in the development of experimental autoimmune vasculitis. Methods: BALB/c mice were immunized with human IgG-ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse IgG-ANCA and other autoantibodies were determined. The mice lungs and kidneys were examined for the development of vasculitis. Levels of interleukin-1β (IL-1β), IL-2, IL- 4, IL-6, interferon γ (IFNγ) and TNFα were determined by ELISA two weeks after immunization of the mice. Results: Mice immunized with human IgG-ANCA developed anti-human IgG-ANCA (= Ab₂) and anti-anti-human IgG-ANCA (mouse IgG-ANCA = Ab₃), while the controls did not develop these antibodies. The mice that were immunized with human IgG-ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. Levels of IL-4, IL-6 and TNFα but not IL-1β, IL-2 and IFNγ were significantly elevated in the mice 2 weeks after immunization with IgG-ANCA. Conclusion: Our results suggest a pathogenic role for IL-4, IL-6 and TNFα in the initiation phase of autoimmune vasculitis. This suggests that a Th2 type immune response is responsible for the initiation of experimental autoimmune lung vasculitis, similar to Wegener's granulomatosis in humans.