Article Text

PDF
Extended report
Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice
  1. Céline Lamacchia1,2,
  2. Emiliana Rodriguez1,2,
  3. Gaby Palmer1,2,
  4. Solenne Vigne1,2,
  5. Praxedis Martin1,2,
  6. Dominique Talabot-Ayer1,2,
  7. Christian A Seemayer3,
  8. Cem Gabay1,2
  1. 1Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland
  2. 2Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland
  3. 3Novartis Pharma AG, Basel, Switzerland
  1. Correspondence to Cem Gabay, Division of Rheumatology, University Hospitals of Geneva, 26 Avenue Beau-Séjour, 1211 Geneva 14, Switzerland; cem.gabay{at}hcuge.ch

Abstract

Objectives To define the cell type (myeloid vs other cells) specific effect of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) deficiency on the acute inflammatory phase of arthritis.

Methods Arthritis was induced by K/BxN serum transfer in wild-type (WT), IL-1Ra-deficient (IL-1Ra−/−) and conditional knockout mice. In the latter, IL-1Ra production was specifically targeted in myeloid cells (IL-1RaΔM) or in both hepatocytes and myeloid cells (IL-1RaΔH+M). Arthritis severity was clinically evaluated and ankle sections were scored for synovial inflammation and cartilage erosion. Quantitative RT-PCR, western blot and immunohistochemical analyses measured expression, localisation and cellular sources of the different IL-1Ra isoforms in arthritic joints.

Results Total and myeloid cell-specific IL-1Ra deficiency was associated with increased arthritis severity, although disease incidence was similar to that of WT mice. Increased clinical scores were associated with exacerbated synovial inflammation. All IL-1Ra isoforms, except for intracellular (ic)IL-1Ra2, were expressed in arthritic joints of WT mice. In contrast, production of secreted (s)IL-1Ra and icIL-1Ra3 isoforms was markedly decreased in arthritic joints of both IL-1RaΔM and IL-1RaΔH+M mice. Immunohistochemical and western blot analyses suggested that the icIL-1Ra1 isoform is produced primarily by synovial fibroblasts.

Conclusion Myeloid cell-derived IL-1Ra, including both sIL-1Ra and icIL-1Ra3 isoforms, controls articular inflammation during the acute phase of K/BxN serum transfer-induced arthritis.

Statistics from Altmetric.com

Footnotes

  • Funding This work was supported by the Swiss National Science Foundation grants 310030-135195 (to CG) and 310030-134691 (to GP), the Rheumasearch Foundation,and the Institute of Arthritis Research.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.