Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro

Michael C.D. Trindade, Yasuharu Nakashima, Martin Lind, Doo Hoon Sun, Stuart B. Goodman, William J. Maloney, David J. Schurman, R. Lane Smith

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin- 4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocytemacrophage colony- stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1 beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte- macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particleinduced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators.

Original languageEnglish
Pages (from-to)797-802
Number of pages6
JournalJournal of Orthopaedic Research
Volume17
Issue number6
DOIs
Publication statusPublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

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