IL-17 NEUTRALIZING ANTIBODY MITIGATES THE FUNCTIONAL AND STRUCTURAL CHANGES IN CIGARETTE SMOKE-INDUCED COPD MODEL

Alyne Riani Moreira¹Camila Uchoa¹Leticia Costa¹Jussara Simao¹Veronica Camargo¹Franciele Lima¹Alex Ferreira Silva¹Suellen Karoline Bezerra¹Cintia Nascimento¹Maria Isabel Cardoso Alonso-Vale²Iolanda de Fátima Lopes Calvo Tibério¹Francine Maria Almeida¹Fernanda Degobbi Tenorio Quirino dos Santos Lopes^1,3*

• ¹University of São Paulo, São Paulo, Brazil
• ²Universidade Federal de Sao Paulo - Campus Sao Paulo, São Paulo, Brazil
• ³Universidade de Sao Paulo, São Paulo, Brazil

Smoking remains the main risk factor for the development of COPD. The inflammatory response mediated by innate and adaptive immune cells has been described in the development and progression of COPD, and the importance of Th17 cytokines has been observed. Studies have shown that blocking IL-17 can reduce inflammation in experimental models of lung injury. This study evaluated the effect of an IL-17 inhibitor in a model of COPD induced by cigarette smoke in C57BL/6 mice. The effects of treatment with IL-17 inhibitor were evaluated in an experimental model of COPD. Mice were exposed to cigarette smoke for 6 months, and treatment with IL-17 inh ibitor was initiated in the 5th month. Four experimental groups were constituted: Control group, animals housed in a vivarium, receiving filtered room air; Control Anti-IL-17 group animals housed in a vivarium, receiving filtered room air and treatment with an anti-IL-17 neutralizing antibody; COPD group, where the animals were exposed to cigarette smoke; and COPD anti-IL-17 group, where the animals were exposed to cigarette smoke and received treatment with an anti-IL-17 neutralizing antibody. In the COPD groups, an increase in mean linear intercept was observed, along with a decrease in tissue elastance and tissue damping, confirming the COPD development.Administration of the IL-17 neutralizing antibody reversed these structural and functional alterations. Additionally, the COPD group exhibited an inflammatory response characterized by increased infiltration of polymorphonuclear and mononuclear cells, and elevated numbers of IL-17-and IL-6-positive cells. These findings were consistent with the increased expression of IL-17 and IL-6 in lung homogenates, as assessed by ELISA.Treatment with the IL-17 neutralizing antibody effectively reversed this inflammatory response by reducing the expression of these inflammatory markers. These results were further supported by the evaluation of RORγt gene expression, which was significantly upregulated in the COPD group. Treatment with the IL-17 neutralizing antibody alleviate this upregulation. Thus, this study demonstrates, for the first time, the effectiveness of IL-17 neutralizing antibody treatment in a cigarette smoke-induced model of COPD, even after lung damage had been established, suggesting the therapeutic potential of IL-17 neutralizing antibodies in COPD.