Beneficial effects of IL-37 after spinal cord injury in mice
Coll Miró, Marina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Francos Quijorna, Isaac (Universitat Autònoma de Barcelona. Institut de Neurociències)
Santos Nogueira, Eva (Universitat Autònoma de Barcelona. Institut de Neurociències)
Torres Espín, Abel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Bufler, P. (Ludwig-Maximilians-Universität München)
Dinarello, CA. (Radboud University Medical Center. Department of Medicine)
López Vales, Rubén (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2016
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.
Grants:	Ministerio de Economía y Competitividad SAF2013-48431-R
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	IL-37 ; Cytokines ; Inflammation ; Neuroprotection ; Spinal cord injury
Published in:	Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, issue 5 (2016) , p. 1411-1416, ISSN 1091-6490

DOI: 10.1073/pnas.1523212113
PMID: 26787859

Postprint 32 p, 2.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles