title: Beneficial effects of IL-37 after spinal cord injury in mice.
abstract: IL-37, a member of the IL-1 family, broadly reduces innate inflammation as well as acquired immunity. Whether the antiinflammatory properties of IL-37 extend to the central nervous system remains unknown, however. In the present study, we subjected mice transgenic for human IL-37 (hIL-37tg) and wild-type (WT) mice to spinal cord contusion injury and then treated them with recombinant human IL-37 (rIL-37). In the hIL-37tg mice, the expression of IL-37 was barely detectable in the uninjured cords, but was strongly induced at 24 h and 72 h after the spinal cord injury (SCI). Compared with WT mice, hIL-37tg mice exhibited increased myelin and neuronal sparing and protection against locomotor deficits, including 2.5-fold greater speed in a forced treadmill challenge. Reduced levels of cytokines (e.g., an 80% reduction in IL-6) were observed in the injured cords of hIL-37tg mice, along with lower numbers of blood-borne neutrophils, macrophages, and activated microglia. We treated WT mice with a single intraspinal injection of either full-length or processed rIL-37 after the injury and found that the IL-37-treated mice had significantly enhanced locomotor skills in an open field using the Basso Mouse Scale, as well as supported faster speed on a mechanical treadmill. Treatment with both forms of rIL-37 led to similar beneficial effects on locomotor recovery after SCI. This study presents novel data indicating that IL-37 suppresses inflammation in a clinically relevant model of SCI, and suggests that rIL-37 may have therapeutic potential for the treatment of acute SCI.
authors.affiliation: Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
authors.forename: Marina
authors.initials: M
authors.lastname: Coll-Miró
authors.affiliation: Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
authors.forename: Isaac
authors.initials: I
authors.lastname: Francos-Quijorna
authors.affiliation: Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
authors.forename: Eva
authors.initials: E
authors.lastname: Santos-Nogueira
authors.affiliation: Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
authors.forename: Abel
authors.initials: A
authors.lastname: Torres-Espin
authors.affiliation: Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, D-80337 Munich, Germany;
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
authors.affiliation: Division of Infectious Diseases, University of Colorado Denver, Aurora, CO 80045; Department of Medicine, Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands cdinare333@aol.com Ruben.Lopez@uab.cat.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Departament de Biologia Cellular, Fisiologia i Immunologia, Institut de Neurociències, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; cdinare333@aol.com Ruben.Lopez@uab.cat.
authors.forename: Rubèn
authors.initials: R
authors.lastname: López-Vales
mesh_terms: D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger
keywords: IL-37; cytokines; inflammation; neuroprotection; spinal cord injury