title: Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha release by human monocyte/macrophages in vitro.
abstract: Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other immunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacrylate (PMMA) particle challenged human monocyte/macrophages in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 microm PMMA particles. Interleukin-10 was added to the monocyte/macrophages with and without the addition of PMMA particles. Interleukin-10-induced alterations in monocyte/macrophage metabolism were determined measuring interleukin-6 and tumor necrosis factor-alpha release by the cells following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-alpha release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-induced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-alpha release was inhibited by 58 and 88% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challenge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-alpha release relative to control cultures. The data presented in this study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.
authors: Orthopaedic Research Laboratory, Stanford University Medical Center, CA 94305-5341, USA.
authors: M C
authors: MC
authors: Trindade
authors: M
authors: M
authors: Lind
authors: Y
authors: Y
authors: Nakashima
authors: D
authors: D
authors: Sun
authors: S B
authors: SB
authors: Goodman
authors: D J
authors: DJ
authors: Schurman
authors: R L
authors: RL
authors: Smith
mesh_terms: D001672:Biocompatible Materials; D001843:Bone Cements / Q000494:pharmacology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D019904:Polymethyl Methacrylate / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; D016895:Culture Media, Serum-Free; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019904:Polymethyl Methacrylate