title: Inhalative IL-10 treatment after bilateral femoral fractures affect pulmonary inflammation in mice.
abstract: BACKGROUND
  Musculoskeletal injuries induce systemic inflammation which often impairs lung function contributing to morbidity. IL-10 has been shown to have a beneficial effect on immune dysfunction and organ damage after different traumatic insults. We sought to investigate the effect of inhalative IL-10 administration on the systemic and pulmonary inflammatory response in a small animal model of bilateral femoral fracture.
  
  
  METHODS
  Male C57/BL6 mice (6 animals per group) were subjected to bilateral femoral fracture and intramedullary nailing followed by inhalative administration of either 50μL PBS (Fx group) or 50μg/kg recombinant mouse IL-10 dissolved in 50μL PBS (FxIL-10 group). All animals were sacrificed at 6, 24, or 72h after fracture induction. Blood samples were collected and analyzed for IL-6, IL-10, KC, and MCP-1 (CCL2) plasma concentrations by Bio-Plex Pro™ assays. Pulmonary infiltration by neutrophils was assessed by myeloperoxidase (MPO) activity (ELISA) and histological analysis of lung tissue. Pulmonary ICAM-1 expression (immunohistochemistry), and pulmonary IL-6 levels (ELISA) were determined.
  
  
  RESULTS
  Inhalative IL-10 administration showed a decrease in the pulmonary infiltration by neutrophils. A significant decrease in the expression of the adhesion molecule ICAM-1 after local IL-10 application was observed. In contrast, local IL-10 administration did not show a significant effect on the systemic inflammatory response.
  
  
  CONCLUSIONS
  Our findings suggest that inhalative IL-10 administration may beneficially modulate the pulmonary microenvironment, in which IL-10 effect on the local ICAM-1 expression seems to play a central role.
authors: Department of Orthopaedic Trauma Surgery, Harald Tscherne Lab for Orthopedic Research, Pauwelsstraβe 30, Aachen, Germany. Electronic address: plichte@ukaachen.de.
authors: Philipp
authors: P
authors: Lichte
authors: Department of Orthopaedic Trauma Surgery, Harald Tscherne Lab for Orthopedic Research, Pauwelsstraβe 30, Aachen, Germany.
authors: Roman
authors: R
authors: Pfeifer
authors: Department of Orthopaedic Trauma Surgery, Faculty of Medicine, RWTH Aachen University, Pauwelsstraβe 30, Aachen, Germany.
authors: Philipp
authors: P
authors: Kobbe
authors: Institute of Anatomy and Cell Biology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraβe 30, Aachen, Germany.
authors: Mersedeh
authors: M
authors: Tohidnezhad
authors: Institute of Anatomy and Cell Biology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraβe 30, Aachen, Germany.
authors: Thomas
authors: T
authors: Pufe
authors: Department of Orthopaedic Trauma Surgery, Harald Tscherne Lab for Orthopedic Research, Pauwelsstraβe 30, Aachen, Germany; Department of Surgery, University of Pittsburgh, Pittsburg, PA, USA.
authors: Khalid
authors: K
authors: Almahmoud
authors: Department of Orthopaedic Trauma Surgery, Harald Tscherne Lab for Orthopedic Research, Pauwelsstraβe 30, Aachen, Germany; Department of Orthopaedic Trauma Surgery, Faculty of Medicine, RWTH Aachen University, Pauwelsstraβe 30, Aachen, Germany.
authors: Frank
authors: F
authors: Hildebrand
authors: Department of Orthopaedic Trauma Surgery, Faculty of Medicine, RWTH Aachen University, Pauwelsstraβe 30, Aachen, Germany.
authors: Hans-Christoph
authors: HC
authors: Pape
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001858:Bone Nails; D018932:Chemokine CCL2 / Q000378:metabolism; D005264:Femoral Fractures / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D018932:Chemokine CCL2; C556062:IL10 protein, mouse; D015850:Interleukin-6; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D009195:Peroxidase
keywords: Fracture; Inflammation; Inhalative IL-10; Mouse model