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-1 beta (IL-1 beta), IL-2, IL-4, IL-6, interferon gamma (IFN gamma) and TNF alpha 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 TNF alpha but not IL-1 beta, IL-2 and IFN gamma 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 TNF alpha 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.