title: Preoperative irradiation for the prevention of heterotopic ossification induces local inflammation in humans.
abstract: Radiation of the hip is an established method to prevent heterotopic ossification (HO) following total hip arthroplasty (THA) but the precise mechanism is unclear. As inflammatory processes are suggested to be involved in the pathogenesis of HO, we hypothesized that the preoperative irradiation impacts local immune components. Therefore, we quantified immune cell populations and cytokines in hematomas resulting from the transection of the femur in two groups of patients receiving THA: patients irradiated preoperatively (THA-X-hematoma: THA-X-H group) in the hip region (7 Gy) in order to prevent HO and patients who were not irradiated (THA-H group) but were postoperatively treated with non-steroidal anti-inflammatory drugs (NSAIDs). Radiation resulted in significantly increased frequencies of T cells, cytotoxic T cells, NKT cells and CD25+CD127- Treg cells, whereas the number of naive CD45RA-expressing cytotoxic T cells was reduced. These results indicate differential immune cell activation, corroborated by our findings of significantly higher concentrations of pro-inflammatory cytokines (e.g., IL-6, IFNγ) and chemokines (e.g., MCP-1, RANTES) in the THA-X-H group as compared to THA-H group. In contrast, the concentration of the angiogenic VEGF was significantly suppressed in the THA-X-H group. We conclude that preoperative irradiation results in significant changes in immune cell composition and cytokine secretion in THA-hematomas, establishing a specific - rather proinflammatory - milieu. This increase of inflammatory activity together with the observed suppression in VEGF secretion may contribute to the prevention of HO.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany. paula.hoff@charite.de
authors.forename: Paula
authors.initials: P
authors.lastname: Hoff
authors.forename: Anastasia
authors.initials: A
authors.lastname: Rakow
authors.forename: Timo
authors.initials: T
authors.lastname: Gaber
authors.forename: Martin
authors.initials: M
authors.lastname: Hahne
authors.forename: Ufuk
authors.initials: U
authors.lastname: Sentürk
authors.forename: Cindy
authors.initials: C
authors.lastname: Strehl
authors.forename: Monique
authors.initials: M
authors.lastname: Fangradt
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.forename: Dörte
authors.initials: D
authors.lastname: Huscher
authors.forename: Tobias
authors.initials: T
authors.lastname: Winkler
authors.forename: Dörte
authors.initials: D
authors.lastname: Matziolis
authors.forename: Georg
authors.initials: G
authors.lastname: Matziolis
authors.forename: Harun
authors.initials: H
authors.lastname: Badakhshi
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000097:blood; D005434:Flow Cytometry; D006406:Hematoma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006615:Hip / Q000528:radiation effects*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008954:Models, Biological; D055611:Natural Killer T-Cells / Q000276:immunology; D009999:Ossification, Heterotopic / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control*; D011182:Postoperative Care; D011300:Preoperative Care; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018925:Chemokines; D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A