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Br J Pharmacol. 2019 Jan 23. doi: 10.1111/bph.14586. [Epub ahead of print]

Neutralization of interleukin-17 rescues amyloid-β-induced neuroinflammation and memory impairment.

Author information

1
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy.
2
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, 80131, Naples, Italy.
3
Institute of Cardiovascular Sciences (ICVS), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.

Abstract

BACKGROUND AND PURPOSE:

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of T helper 17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies, however the role of the main cytokine, IL-17, has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by intracerebroventricular (ICV) or intranasal (IN) routes on amyloid-β-induced neuroinflammation and memory impairment in mice.

EXPERIMENTAL APPROACH:

Amyloid-β (Aβ)1-42 was injected into cerebral ventricle of adult CD1 mice. These mice received IL-17Ab via ICV either at 1 hour prior to Aβ1-42 injection or IN 5 and 12 days after Aβ1-42 injection. After 7- and 14-days of Aβ1-42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas.

KEY RESULTS:

Remarkably, ICV pre-treatment with IL-17Ab remarkably reduced Aβ1-42 -induced neurodegeneration, improved memory function and prevented the increase of pro-inflammatory mediators in a dose dependent manner at 7- and 14-days. Similarly, the double IN administration of IL-17Ab after Aβ1-42 injection reduced neurodegeneration, memory decline and the levels of pro-inflammatory mediators and cytokines.

CONCLUSION AND IMPLICATIONS:

These findings suggest that IL-17Ab reduces neuroinflammation and behavioral symptoms induced by Aβ. The efficacy of IL-17Ab IN administration in reducing Aβ1-42 neurodegeneration points to a possible future therapeutic approach in patients with AD.

KEYWORDS:

Alzheimer; IL-17; Immunotherapy; Intranasal; Neuroinflammation

PMID:
30673121
DOI:
10.1111/bph.14586

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