Popis: |
Aims: Studies suggest that IL17 modulates inflammatory and infectious responses. Objectives: To evaluate anti-IL17 treatment in an asthma animal model exacerbated by LPS. Methods: we studied hyperresponsiveness, inflammation, NO-arginase and oxidative stress pathways, remodeling, Rho-kinase 1 and 2, arginase 1 and NFKB in airways of 36 BALB/c male mice repeatedly exposed to ovalbumin and treated or not with anti IL17. Twenty-four hours before the end of experimental protocol a group received LPS (5mg/kg). Results: OVA-LPS-antiIL17 showed: decrease in %Ers-Mch(47.3±4.2cmH 2 O/L/s), %Rrs-Mch(36.7±4.2cmH2O/L/s), eosinophils (7.8±0.4) and neutrophils (1.5±0.2)-10 4 cells/mL in BALF, CD4+(3.1±0.3%), CD8+(2.4±0.3), IL2(1.9±0.1), IL4(4.8±0.7), IL5(3.3±0.7), IL6(2.2±0.3), IL10(2.9±0.3), IL13(14.6±0.9), IL17(5.7±0.9), TNFα(6.3±1.3), MMP9(10.8±1.1), MMP12(3.1±0.5), TIMP1(3.8±0.6), TGFβ1(11.3±1.3), TARC (4.7±0.35), iNOS(5.2±0.5), NFκB(3.4±0.5), Rho-kinase 1(7.8±0.3) Rho-kinase 2(17.9±1.3) positive cells/10 4 μm 2 , collagen fibers subtypes I(22.9±0.6%), collagen fibers III(10.2±1.1%), actin(27.6±3.1%), decorin (2.0±0.5%), lumican(15.9±1.1%), biglican(9.4±0.6%), fibronectin(3.5±0.6%), eotaxin(0.3±0.0%), PGF2α(9.5±0.9%) contents, RT-PCR for IL-6(0.7±0.1) and arginase 1(2.95±1.5) mRNA levels(UA) compared to OVA-LPS (p Conclusions: IL17 is involved in the control of hyperresponsiveness, Th1/Th2/Th17 inflammation, chemokine expression, remodeling, NO-arginase and oxidative stress pathways in an asthma model exacerbated by LPS. These effects are associated to NFkb and Rho-kinase 1 activation. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP. |