IL-4 alone and in combination with IL-10 protects against blood-induced cartilage damage

Osteoarthritis Cartilage. 2012 Jul;20(7):764-72. doi: 10.1016/j.joca.2012.04.002. Epub 2012 Apr 11.

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.

Design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Chondrocytes / drug effects
  • Chondrocytes / pathology
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Drug Synergism
  • Female
  • Hemarthrosis / complications*
  • Hemarthrosis / metabolism
  • Hemarthrosis / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / pharmacology*
  • Male
  • Middle Aged
  • Proteoglycans / biosynthesis
  • Receptors, Interleukin-10 / biosynthesis
  • Receptors, Interleukin-4 / biosynthesis
  • Tissue Culture Techniques
  • Up-Regulation

Substances

  • Cytokines
  • Inflammation Mediators
  • Proteoglycans
  • Receptors, Interleukin-10
  • Receptors, Interleukin-4
  • Interleukin-10
  • Interleukin-4