title: Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles.
abstract: Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.
authors.affiliation: Division of Orthopaedic Surgery, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA. goodbone@stanford.edu
authors.forename: Stuart
authors.initials: S
authors.lastname: Goodman
authors.forename: Michael
authors.initials: M
authors.lastname: Trindade
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Mel
authors.initials: M
authors.lastname: Lee
authors.forename: Neal
authors.initials: N
authors.lastname: Wang
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikenou
authors.forename: Ippe
authors.initials: I
authors.lastname: Matsuura
authors.forename: Keita
authors.initials: K
authors.lastname: Miyanishi
authors.forename: Nora
authors.initials: N
authors.lastname: Fox
authors.forename: Donald
authors.initials: D
authors.lastname: Regula
authors.forename: Mark
authors.initials: M
authors.lastname: Genovese
authors.forename: John
authors.initials: J
authors.lastname: Klein
authors.forename: Dan
authors.initials: D
authors.lastname: Bloch
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D039564:Integrin alphaV / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D010006:Osteoblasts / Q000502:physiology; D010316:Particle Size; D011095:Polyethylenes / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D013977:Tibia / Q000254:growth & development; D014025:Titanium
chemical_list: D039564:Integrin alphaV; D011095:Polyethylenes; D011994:Recombinant Proteins; C111601:ultra-high molecular weight polyethylene; D016753:Interleukin-10; D014025:Titanium; D000469:Alkaline Phosphatase