title: A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients.
abstract: Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. paula.hoff@charite.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. paula.hoff@charite.de.|Department of Orthopedics, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany. paula.hoff@charite.de.|Endokrinologikum Berlin, 10117 Berlin, Germany. paula.hoff@charite.de.
authors.forename: Paula
authors.initials: P
authors.lastname: Hoff
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. gaber@drfz.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. gaber@drfz.de.|Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany. gaber@drfz.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Gaber
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. strehl@drfz.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. strehl@drfz.de.
authors.forename: Cindy
authors.initials: C
authors.lastname: Strehl
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. jakstadt@drfz.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. jakstadt@drfz.de.
authors.forename: Manuela
authors.initials: M
authors.lastname: Jakstadt
authors.affiliation: German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. holger.hoff@icloud.com.
authors.forename: Holger
authors.initials: H
authors.lastname: Hoff
authors.affiliation: Julius Wolff Institute, Charité University Hospital, 13353 Berlin, Germany. katharina.schmidt-bleek@charite.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. annemarie.lang@charite.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. annemarie.lang@charite.de.|Berlin-Brandenburg School for Regenerative Therapies (BSRT), 13353 Berlin, Germany. annemarie.lang@charite.de.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Lang
authors.affiliation: Department of Orthopedics, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany. e.roehner@krankenhaus-eisenberg.de.
authors.forename: Eric
authors.initials: E
authors.lastname: Röhner
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. huscher@drfz.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. huscher@drfz.de.
authors.forename: Dörte
authors.initials: D
authors.lastname: Huscher
authors.affiliation: Department of Orthopedics, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany. g.matziolis@krankenhaus-eisenberg.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Matziolis
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. gerd.burmester@charite.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. gerd.burmester@charite.de.
authors.forename: Gerd-Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Department of Orthopedics, University Hospital Heidelberg, 69118 Heidelberg, Germany. gerhard.schmidmaier@med.uni-heidelberg.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmidmaier
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany. carsten.perka@charite.de.|Center for Musculoskeletal Surgery, Charité University Hospital, 10117 Berlin, Germany. carsten.perka@charite.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany. georg.duda@charite.de.|Julius Wolff Institute, Charité University Hospital, 13353 Berlin, Germany. georg.duda@charite.de.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10117 Berlin, Germany. frank.buttgereit@charite.de.|German Rheumatism Research Center (DRFZ), 10117 Berlin, Germany. frank.buttgereit@charite.de.|Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany. frank.buttgereit@charite.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D017102:Fracture Healing / Q000276:immunology*; D050723:Fractures, Bone / Q000276:immunology / Q000473:pathology; D006406:Hematoma / Q000276:immunology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016867:Immunocompromised Host; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic; D010641:Phenotype
chemical_list: D043925:Angiogenesis Inducing Agents; D016207:Cytokines; D018836:Inflammation Mediators
keywords: bone healing; chemokines; cytokines; fracture healing; fracture hematoma; immune cells; immunologically restricted patients; inflammation