Anti IL-17 with or without Rho kinase inhibitor in mice with chronic allergic pulmonary inflammation

Aims: Asthmatics have elevated levels of interleukin (IL)-17 and Rho-kinase protein activity in their airways associated to the modulation of inflammatory mediators and cells. Objectives: To study the effects of anti-IL-17 neutralizing antibody and Rho-kinase inhibitor treatments, associated or not, in mice with chronic allergic inflammation. Methods: sensitization and induction of pulmonary inflammation by ovalbumin has the duration of 28 days. Anti-IL-17A neutralizing antibody (clone 50104-7.5/µg/dose) was administered intraperitoneally and Rho-kinase inhibitor intranasally (Y-27632-10 mg/kg), 1h before each ovalbumin challenge (22, 24, 26 and 28/days). Results: OVA-Rhoi-anti-IL17 showed a decrease in: %Rrs after Mch (9.4±1.4%),%Ers(22.0±3.3%), eosinophils(0.04±0.4), macrophages(0.05±0.009)104cells/mL in BALF, CD4+(2.3±0.3), CD8+(4.6±0.8), IL6(1.1±0.3), IL13(1,6±0,7), IL17(1.0±0.1), TNFα(1.5±0.2), Rho-kinase-1(0.01±0.01) positive cells/104μm2 in airways, collagen fibers (5.8±0.4%), PGF2α(5.2±1.3%) contents, RT-PCR for VAChT(7.2±1.5) and arginase-1(0.9±0.2) mRNA levels (UA) compared to OVA (p<0.05 for all comparisons). OVA-Rhoi and OVA-anti-IL-17 also have a decrease in all parameters compared to OVA (p<0.05). OVA-Rhoi-anti-IL17 potentates the decrease of %Rrs to Mch, CD8+ and TNFα positive cells in airways compared to OVA-Rhoi and OVA-Anti-IL17 (p<0.05). Conclusions: Anti-IL-17 or Rho-kinase inhibitor modulates airway responsiveness, inflammation and remodeling. The association of these drugs potentates the control of hyperresponsiveness and some inflammatory parameters in relation to isolated treatments in this animal model. Financial Support: FAPESP, CNPq, LIM-20-HC-FMUSP.