호산구성 만성 비부비동염 동물모델에서 아바타셉트의 치료효과
Therapeutic Effect of Abatacept (Cytotoxic T Lymphocyte Antigen 4-Fragment Crystallizable) in a Mouse Model of Eosinophilic Chronic Rhinosinusitis
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Background and Objectives Abatacept is a chimeric protein that combines the Fc region of human immunoglobulin G1 with human cytotoxic T-lymphocyte-associated protein-4. Abatacept is increasingly used for inflammatory disease including rheumatoid arthritis. How- ever, the impact of abatacept on chronic rhinosinusitis remains largely unexplored. This study aimed to evaluate the therapeutic potential of abatacept in a mouse model of eosinophilic chronic rhinosinusitis (ECRS). Materials and Method The mice were assigned to four different treatment groups: control, ECRS, abatacept-treated (Aba), and dexamethasone-treated (Dexa) groups. To assess the ef- fects of abatacept in the mouse model of ECRS, several techniques were employed, including hematoxylin and eosin staining, Periodic acid-Schiff staining, real-time quantitative poly- merase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Results Epithelial thickness, the number of goblet cells and eosinophil infiltration in the na- sal mucosa, was significantly decreased in the Aba and Dexa groups compared with the ECRS group. The concentrations of interleukin (IL)-10, IL-4, and IL-5 in the nasal lavage fluid were significantly reduced in both the Aba and Dexa groups compared to the ECRS group. Similar- ly, the expression levels of IL-4, IL-5, IL-10, IL-13, IL-17A, and interferon gamma in the nasal mucosa were markedly lower in the Aba and Dexa groups than in the ECRS group. Conclusion Abatacept treatment reduced the number of Th immune response-associated molecules and cytokines, resulting in the suppression of nasal polyp formation and mucosal inflammation in ECRS mice. Based on these results, Abatacept could be considered a poten- tial therapeutic option for patients with ECRS.
Abstract
Background and Objectives Abatacept is a chimeric protein that combines the Fc region of human immunoglobulin G1 with human cytotoxic T-lymphocyte-associated protein-4. Abatacept is increasingly used for inflammatory disease including rheumatoid arthritis. How- ever, the impact of abatacept on chronic rhinosinusitis remains largely unexplored. This study aimed to evaluate the therapeutic potential of abatacept in a mouse model of eosinophilic chronic rhinosinusitis (ECRS). Materials and Method The mice were assigned to four different treatment groups: control, ECRS, abatacept-treated (Aba), and dexamethasone-treated (Dexa) groups. To assess the ef- fects of abatacept in the mouse model of ECRS, several techniques were employed, including hematoxylin and eosin staining, Periodic acid-Schiff staining, real-time quantitative poly- merase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Results Epithelial thickness, the number of goblet cells and eosinophil infiltration in the na- sal mucosa, was significantly decreased in the Aba and Dexa groups compared with the ECRS group. The concentrations of interleukin (IL)-10, IL-4, and IL-5 in the nasal lavage fluid were significantly reduced in both the Aba and Dexa groups compared to the ECRS group. Similar- ly, the expression levels of IL-4, IL-5, IL-10, IL-13, IL-17A, and interferon gamma in the nasal mucosa were markedly lower in the Aba and Dexa groups than in the ECRS group. Conclusion Abatacept treatment reduced the number of Th immune response-associated molecules and cytokines, resulting in the suppression of nasal polyp formation and mucosal inflammation in ECRS mice. Based on these results, Abatacept could be considered a poten- tial therapeutic option for patients with ECRS.
