Arthritis in mice that are deficient in interleukin-1 receptor antagonist is dependent on genetic background
Arthritis in mice that are deficient in interleukin-1 receptor antagonist is dependent on genetic background
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DOI：
10.1002/art.21481
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发表时间：
2005-12-01
影响因子：
--
通讯作者：
Stuart, JM
中科院分区：
文献类型：
--
作者：
Zhou, F;He, XW;Stuart, JM
Objective. To determine the effect of deletion of interleukin-1 receptor antagonist (IL-1Ra) protein in an animal model of rheumatoid arthritis.Methods. BALB/c mice deficient in IL-1Ra (IL-1Ra(-/-)) were bred with collagen-induced arthritis (CIA)-susceptible DBA/1 mice and B10 mice transgenic for HLA-DRBl*0101 (B10.DR1). After generation of IL-1Ra(-/-) mice on the DBA/1 and B10.DR1 backgrounds, the mice were observed for the development of spontaneous arthritis and immunized for induction of CIA.Results. We found that although BALB/c mice deficient in IL-1Ra (BALB/c(-/-)) spontaneously developed chronic inflammatory arthritis, DBA/1 IL-1Ra-deficient (DBA/1(-/-)) and B10.DRI IL-IRa-deficient (B10.DR1(-/-)) mice did not. Splenocytes from BALB/c(-/-) mice produced elevated levels of IL-2, IL-4, IL-6, IL-10, IL-17, and granulocyte-macrophage colony-stimulating factor in response to anti-CD3 stimulation. After immunization with type II collagen (CII), DBA/1(-/-) and B1O.DR1(-/-) mice had a significantly earlier onset of CIA, and with increased severity compared with IL-1Ra(+/+) mice. Immunization of BALB/c(-/-) mice with CII did not aggravate spontaneous arthritis. All of the immunized mice developed antibodies to CII that correlated with arthritis severity. Levels of antibody to CII in the BALB/c(-/-) strain were relatively low.Conclusion. These data indicate that the spontaneous arthritis of IL-1Ra deficiency is highly dependent on non-major histocompatibility complex genes and that autoimmunity to CH is not the major disease-inducing event. Class II immune response genes are more important for the regulation of CIA, and although these 2 models of arthritis share many pathogenic mechanisms, they also have significant differences.
