Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced arthritis by a different mode of action from that of interleukin-1 receptor antagonist

Arthritis Rheum. 2005 Jul;52(7):2202-11. doi: 10.1002/art.21108.


Objective: To discern the mode of interleukin-1 (IL-1) inhibition of soluble IL-1 receptor accessory protein (sIL-1RAcP) by comparison with IL-1 receptor antagonist (IL-1Ra) in arthritis.

Methods: Adenoviral vectors encoding either sIL-1RAcP or IL-1Ra were administered systemically before onset of collagen-induced arthritis in DBA/1 mice. Anti-bovine type II collagen IgG and IL-6 were quantified in serum. Proliferative response of splenic T cells was determined in the presence of sIL-1RAcP or IL-1Ra. The effect on IL-1 inhibition of recombinant sIL-1RAcP and IL-1Ra was further examined in vitro, using NF-kappaB luciferase reporter cell lines. Quantitative polymerase chain reaction was used to determine the relative messenger RNA expression of the IL-1 receptors.

Results: Adenoviral overexpression of both sIL-1RAcP and IL-1Ra resulted in amelioration of the collagen-induced arthritis. Both IL-1 antagonists reduced the circulating levels of antigen-specific IgG2a antibodies, but only IL-1Ra was able to inhibit lymphocyte proliferation. By using purified lymphocyte populations derived from NF-kappaB reporter mice, we showed that sIL-1RAcP inhibits IL-1-induced NF-kappaB activity in B cells but not T cells, whereas IL-1Ra inhibited IL-1 on both cell types. A study in a panel of NF-kappaB luciferase reporter cells showed that the sIL-1RAcP inhibits IL-1 signaling on cells expressing either low levels of membrane IL-1RAcP or high levels of IL-1RII.

Conclusion: We show that the sIL-1RAcP ameliorated experimental arthritis without affecting T cell immunity, in contrast to IL-1Ra. Our results provide data in support of receptor competition by sIL-1RAcP as an explanation for the different mode of IL-1 antagonism in comparison with IL-1Ra.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / therapy*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cattle
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Expression
  • Genetic Therapy*
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / metabolism
  • Interleukin-1 Receptor Accessory Protein
  • Male
  • Mice
  • Mice, Inbred DBA
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / genetics*
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Il1rap protein, mouse
  • Interleukin-1
  • Interleukin-1 Receptor Accessory Protein
  • NF-kappa B
  • Proteins
  • RNA, Messenger
  • Receptors, Interleukin-1