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.


CONCLUSIONS
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.
Tomer
Y
Y
Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel.
Barak
V
V
Gilburd
B
B
Shoenfeld
Y
Y
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001323:Autoantibodies / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000494:pharmacology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D007375:Interleukin-1 / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma