title: IL-4 alone and in combination with IL-10 protects against blood-induced cartilage damage.
abstract: OBJECTIVE
  It has been reported that interleukin (IL)-10 limits blood-induced cartilage damage. Our aim was to study the effect of IL-4 alone and in combination with IL-10 on blood-induced cartilage damage.
  
  
  METHODS
  Healthy human full thickness cartilage explants were cultured for 4 days in the presence of 50% v/v blood. IL-4, IL-10, or a combination of both cytokines was added during blood exposure. Cartilage matrix turnover was determined after a recovery period; additionally cytokine production, chondrocyte apoptosis, and expression of the IL-4 and IL-10 receptors were analyzed directly after exposure.
  
  
  RESULTS
  Blood-induced damage to the cartilage matrix was limited by IL-4 in a dose-dependent way (P<0.05). Also IL-10 limited this damage, although to a lesser extent (P<0.03). The effect of IL-4 plus IL-10 was more pronounced and protective than IL-10 alone (P<0.05). Production of IL-1β and tumor necrosis factor (TNF)-α was limited by both IL-4 and IL-10 (P<0.05), but more strongly by IL-4. Blood-induced apoptosis of chondrocytes was limited by IL-4 and the combination, and not by IL-10 alone. No direct beneficial effect of IL-4 or IL-10 on cartilage was found, however, the chondrocyte receptor expression of both cytokine receptors was upregulated by exposure to blood.
  
  
  CONCLUSIONS
  This study demonstrates that IL-4 alone and in combination with IL-10 prevents blood-induced cartilage damage. Expectedly, anti-inflammatory effects on monocytes in the blood fraction and protective effects on chondrocytes are both involved. IL-4 in combination with IL-10 might be used to prevent blood-induced joint damage as a result of trauma or surgery.
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. M.E.R.vanMeegeren@umcutrecht.nl
authors.forename: M E R
authors.initials: ME
authors.lastname: van Meegeren
authors.forename: G
authors.initials: G
authors.lastname: Roosendaal
authors.forename: N W D
authors.initials: NW
authors.lastname: Jansen
authors.forename: M J G
authors.initials: MJ
authors.lastname: Wenting
authors.forename: A C W
authors.initials: AC
authors.lastname: van Wesel
authors.forename: J A G
authors.initials: JA
authors.lastname: van Roon
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D005260:Female; D006395:Hemarthrosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis; D053701:Receptors, Interleukin-10 / Q000096:biosynthesis; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis; D046509:Tissue Culture Techniques; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011509:Proteoglycans; D053701:Receptors, Interleukin-10; D019948:Receptors, Interleukin-4; D016753:Interleukin-10; D015847:Interleukin-4