title: Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice.
abstract: OBJECTIVE
  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-1Ra(ΔM)) or in both hepatocytes and myeloid cells (IL-1Ra(ΔH+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-1Ra(ΔM) and IL-1Ra(ΔH+M) mice. Immunohistochemical and western blot analyses suggested that the icIL-1Ra1 isoform is produced primarily by synovial fibroblasts.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, University Hospitals of Geneva, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Lamacchia
authors.forename: Emiliana
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.forename: Solenne
authors.initials: S
authors.lastname: Vigne
authors.forename: Praxedis
authors.initials: P
authors.lastname: Martin
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.forename: Christian A
authors.initials: CA
authors.lastname: Seemayer
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D018450:Disease Progression; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism*; D020033:Protein Isoforms / Q000172:deficiency / Q000502:physiology; D044967:Serum; D012720:Severity of Illness Index; D013585:Synovitis / Q000378:metabolism / Q000473:pathology
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D020033:Protein Isoforms