title: Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels.
abstract: OBJECTIVE
  To investigate whether intraarticular (IA) glucocorticoid (GC) therapy diminishes synovial cell infiltration, vascularity, expression of proinflammatory cytokines, and adhesion molecule levels in patients with chronic arthritides.
  
  
  METHODS
  Thirty-one patients with chronic arthritides received a single IA injection of triamcinolone hexacetonide to treat active large-joint inflammation. Synovial biopsy specimens were obtained with arthroscopic guidance before and 9-15 days after injection. The presence of T lymphocytes, macrophages, intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), the pan-endothelial marker CD31, and the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor (TNF), and high mobility group box chromosomal protein 1 (HMGB-1) was studied by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  IA GC treatment resulted in good clinical response in 29 of 31 joints. After therapeutic intervention, the number of synovial T lymphocytes declined, whereas the number of macrophages remained unchanged. Overall synovial protein expression of TNF, IL-1beta, extranuclear HMGB-1, VEGF, and ICAM-1 was reduced at followup tissue sampling, while no significant effects were observed regarding vascularity. In contrast, expression of IL-1alpha, VEGF, and cytoplasmic HMGB-1 protein in vascular endothelial cells was not affected. GC therapy down-regulated levels of messenger RNA encoding IL-1alpha and IL-1beta, but not TNF or HMGB-1.
  
  
  CONCLUSIONS
  Synovial cell infiltration and proinflammatory cytokine expression were affected in a multifaceted manner by IA GC treatment. Marked reduction of synovial T lymphocytes, TNF, IL-1beta, extranuclear HMGB-1, ICAM-1, and VEGF occurred in association with beneficial clinical effects. Unexpectedly, macrophage infiltration and proinflammatory endothelial cytokine expression remained unchanged. These findings may reflect mechanisms controlling the transiency of clinical improvement frequently observed after IA GC injection.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: af Klint
authors.forename: Cecilia
authors.initials: C
authors.lastname: Grundtman
authors.forename: Marianne
authors.initials: M
authors.lastname: Engström
authors.forename: Anca Irinel
authors.initials: AI
authors.lastname: Catrina
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Makrygiannakis
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Ulf
authors.initials: U
authors.lastname: Andersson
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Ulfgren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D001808:Blood Vessels / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005938:Glucocorticoids / Q000008:administration & dosage*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007270:Injections, Intra-Articular; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D013585:Synovitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D024243:HMGB1 Protein; D012333:RNA, Messenger; D014222:Triamcinolone Acetonide; C005900:triamcinolone hexacetonide