title: Anti-Inflammatory Effects of IL-27 in Zymosan-Induced Peritonitis: Inhibition of Neutrophil Recruitment Partially Explained by Impaired Mobilization from Bone Marrow and Reduced Chemokine Levels.
abstract: Rapid activation of the innate immune system is critical for an efficient host response to invading pathogens. However, the inflammatory reaction has to be strictly controlled to minimize harmful immunopathology. A number of mediators including the cytokine interleukin-27 (IL-27) appear to be responsible for limitation and resolution of inflammation. Despite increasing knowledge of its suppressive effects on T cells, the influence on neutrophils and macrophages is poorly understood. To determine the role of IL-27 in innate immune responses we analysed the effect of IL-27 in a T cell independent model of zymosan-induced peritonitis. Early administration of recombinant IL-27 strongly reduced the number of neutrophils recruited to the peritoneal cavity after zymosan application as well as the neutrophil frequency in the blood. Simultaneously, IL-27 reduced the release of neutrophils from the bone marrow upon inflammation. Although cytokine levels were not affected by IL-27 treatment, the levels of the chemokines KC, MCP-1 and MIP-1α in the peritoneal fluid were strongly decreased. These findings demonstrate that IL-27 is able to control mobilisation and recruitment of neutrophils into the peritoneal cavity and identify a novel mechanism to limit inflammation caused by innate immune cells.
authors.affiliation: Department of Neurology and Experimental Neurology, Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Watzlawick
authors.affiliation: Department of Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Elisabeth E
authors.initials: EE
authors.lastname: Kenngott
authors.affiliation: Department of Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
authors.forename: Francesca Diane M
authors.initials: FD
authors.lastname: Liu
authors.affiliation: Department of Neurology and Experimental Neurology, Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Neurology, Spinal Cord Injury Division, The Neuroscience Institute, The Ohio State University, Wexner Medical Center, Columbus, Ohio, United States of America; Department of Neuroscience and Center for Brain and Spinal Cord Repair, Department of Physical Medicine and Rehabilitation, The Neuroscience Institute, The Ohio State University, Wexner Medical Center, Columbus, Ohio, United States of America.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schwab
authors.affiliation: Department of Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D064094:Interleukin-27 / Q000378:metabolism* / Q000494:pharmacology; D007958:Leukocyte Count; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D015054:Zymosan / Q000009:adverse effects
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D064094:Interleukin-27; D015054:Zymosan