Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 5, Pages 1411-1416Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1523212113
Keywords
IL-37; spinal cord injury; inflammation; neuroprotection; cytokines
Categories
Funding
- Fundacio La Marato
- Spanish Ministry of Economy and Competitiveness [SAF2013-48431-R]
- International Foundation for Research in Paraplegia
- Fondo de Investigacion Sanitaria of Spain [Red de Terapia Celular (TERCEL)]
- Fondo de Investigacion Sanitaria of Spain [Centro de Investigacion Biomedica en Red, Enfermedades Neurodegenerativas (CIBERNED)]
- National Institutes of Health [AI-15614]
- Deutsche Forschungsgemeinschaft [BU 1222/3-3]
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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.
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