Effects of Anti-Il17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS

Aims: Th2 inflammation plays a central role in asthma. Cytokine IL17 has been examined to be involved in both asthma and in infectious diseases. Objectives: To estimate the effects of anti-IL17 therapy on distal lung of an asthma model exacerbated by LPS. Methods: BALB/c mice were sensitized with ovalbumin followed by treatment with or without anti-IL17. Twenty-four hours prior to the end of the 29-day experimental protocol, the groups received LPS (0.1mg/ml-intratracheally). We evaluated bronchoalveolar lavage fluid (BALF), inflammatory cytokines, extracellular matrix remodelling, oxidative stress, NFKB and Rho-kinase 1 and 2. Results: OVA-LPS anti-IL-17 showed a decrease in neutrophils(0.02±0.0), eosinophils(0.9±0.2), macrophages(0.07±0.0)-104cells/mL in BALF, FOXP3 (5.7±0.9), dendritic cells (2.0±0.2), CD4+(2.4±0.3), CD8+(1.9±0.3), IL2 (1.9±0.1), IL4 (10.8±1.0), IL5 (2.0±0.3), IL6 (2.1±0.1), IL10 (1.7±0.1), IL13 (2.6±0.5), IL17 (5.7±0.9), TNFα (0.7±0.1), MMP9 (9.7±0.4), MMP12 (1.6±0.2), TIMP1 (3.9±0.5), TGFβ1 (8.3±0.7), TARC (2.4±0.4), TGFβ(8.3±0.7), iNOS(3.2±0.3), NFKB (1.7±0.3), ROCK1 (3.3±0.3), ROCK2(8.3±0.8) positive cells/104μm2, collagen Fibers-I(20.0±0.7%), collagen Fibers-III(7.8±0.7%), actin(6.9±1.6%), decorin (7.8±0.7%), lumican(15.3±0.5%), biglican(5.0±0.6%), fibronectin(10.2±0.7%), PGF2α (0.2±0.0%) contents, RT-PCR for IL-6 (0.71±0.18 mRNA levels/UA) compared to OVA-LPS, p<0.05 for all comparisons, except for macrophages. Conclusions: Inhibition of IL-17 contributes to control of Th1/Th2/Th17 inflammation, extracellular matrix remodelling and oxidative stress in asthma model exacerbated by LPS. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP.