Journal
ELIFE
Volume 11, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.75889
Keywords
neurodegeneration; neuroinflammation; memory; hippocampus; cytokine; Mouse
Categories
Funding
- DFG [AI- 15614]
- Helmholtz- Gemeinschaft, Zukun-ftsthema Immunology and Inflammation
- NIH
- [SFB854]
- [ZT- 0027]
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IL-37 has immunomodulatory effects in the central nervous system, protecting neuronal structure and function, inhibiting microglial activation, enhancing long-term potentiation, and exerting anti-inflammatory effects in chronic neuroinflammatory conditions like Alzheimer's disease.
The anti-inflammatory cytokine interleukin-37 (IL-37) belongs to the IL-1 family but is not expressed in mice. We used a human IL-37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Previous studies reveal an immunomodulatory role of IL-37, which can be characterized as an important suppressor of innate immunity. Here, we examined the functions of IL-37 in the central nervous system and explored the effects of IL-37 on neuronal architecture and function, microglial phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. In wild-type mice, decreased spine density, activated microglial phenotype and impaired long-term potentiation (LTP) were observed after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimer's disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that expression of IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent loss of cognitive abilities in a mouse model of AD.
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