Inhibitory effects of recombinant IL-4 and recombinant IL-13 on UHMWPE-induced bone destruction in the murine air pouch model

J Surg Res. 2013 Apr;180(2):e73-81. doi: 10.1016/j.jss.2012.04.016. Epub 2012 Apr 28.

Abstract

Purpose: We administered recombinant interleukin (IL)-4 and recombinant IL-13 locally into the air pouch of mice to improve bone resorption induced by ultra-high-molecular-weight polyethylene (UHMWPE) particles.

Methods: Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of calvaria from a syngeneic mouse donor. We stimulated the bone-implanted pouches with the UHMWPE suspension. We divided UHMWPE-containing mice into four study groups to receive injections of phosphate-buffered saline (control), IL-4 alone, IL-13 alone, or IL-4 and IL-13 into the pouches. We harvested the tissues at 14 d after treatment for molecular and histological analyses.

Results: The inhibitory effect of IL-4 was stronger than that of IL-13 toward osteoclast differentiation and osteoblast for the induction of osteoprotegerin production and down-regulation of receptor for activation of nuclear factor-κB ligand production. Furthermore, the combined treatment with both IL-4 and 1L-13 had a more important role in inhibiting bone resorption in these pouches with UHMWPE stimulation, compared with IL-4 or IL-13 treatment alone.

Conclusions: Local administration of recombinant IL-4 and IL-13 may be a feasible and effective therapeutic candidate to treat or prevent wear debris-associated osteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / analysis
  • Animals
  • Cell Differentiation / drug effects
  • Disease Models, Animal
  • Female
  • Interleukin-13 / therapeutic use*
  • Interleukin-4 / therapeutic use*
  • Isoenzymes / analysis
  • Mice
  • Mice, Inbred BALB C
  • Osteoclasts / cytology
  • Osteoclasts / drug effects
  • Osteolysis / drug therapy*
  • Polyethylenes / toxicity*
  • Receptor Activator of Nuclear Factor-kappa B / analysis
  • Recombinant Proteins / therapeutic use
  • Tartrate-Resistant Acid Phosphatase

Substances

  • Interleukin-13
  • Isoenzymes
  • Polyethylenes
  • Receptor Activator of Nuclear Factor-kappa B
  • Recombinant Proteins
  • Tnfrsf11a protein, mouse
  • ultra-high molecular weight polyethylene
  • Interleukin-4
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase