title: Characterization of macrophage polarizing cytokines in the aseptic loosening of total hip replacements.
abstract: Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle-induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT-PCR, the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and IL-17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN-γ or IL-4 could be identified. IL-17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up-regulation of IL-10, M-CSF, IL-8, CCL2-4, CXCL9-10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF-α, IL-1β, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri-implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines.
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Eemeli
authors.initials: E
authors.lastname: Jämsen
authors.forename: Vesa-Petteri
authors.initials: VP
authors.lastname: Kouri
authors.forename: Juri
authors.initials: J
authors.lastname: Olkkonen
authors.forename: Andrej
authors.initials: A
authors.lastname: Cör
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000295:instrumentation*; D016764:Cell Polarity / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D005260:Female; D006621:Hip Joint / Q000473:pathology; D006622:Hip Prosthesis; D006801:Humans; D008264:Macrophages / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000601:surgery; D011475:Prosthesis Failure; D012086:Reoperation; D012189:Retrospective Studies; D013583:Synovial Membrane / Q000473:pathology
chemical_list: D016207:Cytokines
keywords: foreign body response; joint replacement; lymphocyte; macrophage polarization; wear debris