Arthritis in mice that are deficient in interleukin-1 receptor antagonist is dependent on genetic background

Fang Zhou, Xiaowen He, Yoichiro Iwakura, Reiko Horai, John Stuart

Research output: Contribution to journalArticle

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Abstract

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-DRB1*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.DR1 IL-1Ra-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 B10.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 CII 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.

Original languageEnglish (US)
Pages (from-to)3731-3738
Number of pages8
JournalArthritis and rheumatism
Volume52
Issue number12
DOIs
StatePublished - Dec 1 2005

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Interleukin-1 Receptors
Arthritis
Experimental Arthritis
Interleukin 1 Receptor Antagonist Protein
Inbred DBA Mouse
Immunization
Genetic Background
HLA-DRB1 Chains
Collagen Type II
Interleukin-17
Antibodies
Granulocyte-Macrophage Colony-Stimulating Factor
Major Histocompatibility Complex
Autoimmunity
Interleukin-4
Interleukin-10
Transgenic Mice
Genes
Interleukin-2
Interleukin-6

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Arthritis in mice that are deficient in interleukin-1 receptor antagonist is dependent on genetic background. / Zhou, Fang; He, Xiaowen; Iwakura, Yoichiro; Horai, Reiko; Stuart, John.

In: Arthritis and rheumatism, Vol. 52, No. 12, 01.12.2005, p. 3731-3738.

Research output: Contribution to journalArticle

Zhou, Fang ; He, Xiaowen ; Iwakura, Yoichiro ; Horai, Reiko ; Stuart, John. / Arthritis in mice that are deficient in interleukin-1 receptor antagonist is dependent on genetic background. In: Arthritis and rheumatism. 2005 ; Vol. 52, No. 12. pp. 3731-3738.
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abstract = "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-DRB1*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.DR1 IL-1Ra-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 B10.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 CII 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.",
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N2 - 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-DRB1*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.DR1 IL-1Ra-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 B10.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 CII 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.

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