Neutralization of IL-17 rescues amyloid-ß-induced neuroinflammation and memory impairment.

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 Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL-17 has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by i.c.v. or intranasal (IN) routes on amyloid-ß (Aß)-induced neuroinflammation and memory impairment in mice. EXPERIMENTAL APPROACH: Aß1-42 was injected into cerebral ventricles of adult CD1 mice. These mice received IL-17Ab via i.c.v. either at 1 h prior to Aß1-42 injection or IN 5 and 12 days after Aß1-42 injection. After 7 and 14 days of Aß1-42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas. KEY RESULTS: Pretreatment with IL-17Ab, given, i.c.v., markedly reduced Aß1-42 -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 Aß1-42 injection reduced neurodegeneration, memory decline, and the levels of proinflammatory mediators and cytokines. CONCLUSION AND IMPLICATIONS: These findings suggest that the IL-17Ab reduced neuroinflammation and behavioural symptoms induced by Aß. The efficacy of IL-17Ab IN administration in reducing Aß1-42 neurodegeneration points to a possible future therapeutic approach in patients with AD. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

Anti-Inflammatory and Anti-Oxidant Activity of Portulaca oleracea Extract on LPS-Induced Rat Lung Injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are classified as two lung complications arising from various conditions such as sepsis, trauma, and lung inflammation. Previous studies have shown that the extract of the leaves of Portulaca oleracea (PO) possesses anti-inflammatory and anti-oxidant activities. In the present study, the effects of PO (50⁻200 mg/kg) and dexamethasone (Dexa; 1.5 mg/kg) on lipopolysaccharide (LPS)-induced ALI were investigated. Subsequentially, the lung wet/dry ratio; white blood cells (WBC); levels of nitric oxide (NO); myeloperoxidase (MPO); malondialdehyde (MDA); thiol groups formation; super oxide dismutase (SOD) and catalase (CAT) activities; and levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, prostaglandin E2 (PGE2), and transforming growth factor (TGF)-ß in the broncho alveolar lavage fluid (BALF) were evaluated in order to demonstrate the anti-oxidant and anti-inflammatory activity of PO. Our results show that PO suppresses lung inflammation by the reduction of IL-ß, IL-6, TNF-α, PGE2, and TGF-ß, as well as by the increase of IL-10 levels. We also found that PO improves the level of WBC, MPO, and MDA, as well as thiol group formation and SOD and CAT activities, compared with the LPS group. The results of our investigation also show that PO significantly decreased the lung wet/dry ratio as an index of interstitial edema. Taken together, our findings reveal that PO extract dose-dependently displays anti-oxidant and anti-inflammatory activity against LPS-induced rat ALI, paving the way for rational use of PO as a protective agent against lung-related inflammatory disease.