Preventive and therapeutic effect of anti-IL-17 in an experimental model of elastase-induced lung injury in C57Bl6 mice

Abstract

COPD is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI IL-17 (ET). On 29th day, animals were anesthetized with thiopental, tracheotomized and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid (BALF) was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti IL-17 decreased respiratory resistance (Rrs) and elastance (Ers), airway resistance (Raw), elastance of pulmonary parenchyma (Htis), eNO, Lm compared to EC. There was reduction in total cells and macrophages in ET compared to EC. Both treatments decreased nuclear factor kappa B (NF-кB), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), neutrophils, IL-1β, isoprostane and IL-17 in airways and alveolar septa, collagen fibers, decorin and lumican in airways, elastic fibers and fibronectin in alveolar septa compared to EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP, and reduction of endothelial nitric oxide synthase (eNOS) in airways in ET. In conclusion, both treatments with anti IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.

Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma–COPD (ACO) model

“…NF-kappaB plays a crucial role in oxidative stress, as excessive activation perpetuates the production of inflammatory mediators in severe asthma and may exacerbate COPD, given its association with TNF-α, IL-8, and other inflammatory cells. Notably, the expression of iNOS and cytokines related to the Th2 and Th17 profiles relies on NF-kappaB transcription ( Fukusaki, 2019 ). In our study, the experimental groups (ACO, ELA, and OVA) exhibited elevated NF-kappaB values, and the treatments were effective in reducing these values in the ACO group.…”

IL-17 Cytokines and Chronic Lung Diseases

“…Similar results were obtained in models of elastase-induced lung damage. Elastase-induced inflammation and loss of lung structure were reduced in IL-17A-deficient mice as well as in mice treated with therapeutic anti-IL-17A antibodies [ 104 , 105 , 106 ]. Moreover, IL-17A deficiency resulted in a decreased apoptosis of alveolar type-II cells in mice exposed to CS for 4 weeks [ 107 ] and an attenuated lymphoid neogenesis in mice exposed to CS for 24 weeks [ 96 ].…”

Th17/Treg Imbalance in Chronic Obstructive Pulmonary Disease: Clinical and Experimental Evidence

“…More recently, the efficiency of treatment with anti-IL-17 has been demonstrated to improve the inflammation observed in asthma (76,77), asthma exacerbated by LPS (78,79) and LPSinduced lung injury (80). In an elastase-induced model of emphysema, it was also demonstrated that both preventive and therapeutic treatment with anti-IL17 improved the evaluated inflammatory parameters in mice, including specific markers for the Th17 response (81).…”