IL-17-neutralizing antibody mitigates functional and structural changes in cigarette smoke-induced COPD model

Area of Science:

• Pulmonology
• Immunology
• Pharmacology

Background:

• Smoking is the primary cause of chronic obstructive pulmonary disease (COPD).
• Inflammatory responses involving immune cells and Th17 cytokines are implicated in COPD development and progression.
• Blocking interleukin-17 (IL-17) has shown promise in reducing lung injury inflammation in experimental models.

Purpose of the Study:

• To evaluate the therapeutic effect of an IL-17 inhibitor in a cigarette smoke-induced COPD mouse model.
• To assess if IL-17 blockade can reverse established lung damage and inflammation in COPD.

Main Methods:

• C57BL/6 mice were exposed to cigarette smoke for 6 months to induce COPD.
• An IL-17-neutralizing antibody treatment was administered during the fifth month of smoke exposure.
• Groups included: Control, Control + anti-IL-17, COPD, and COPD + anti-IL-17. Lung structure, function, and inflammatory markers (IL-17, IL-6, RORγt) were assessed.

Main Results:

• COPD model mice showed increased mean linear intercept, decreased tissue elastance and damping, confirming COPD.
• IL-17 antibody treatment reversed these structural and functional lung changes.
• Treatment reduced inflammatory cell infiltration, IL-17, IL-6 expression, and RORγt gene expression in COPD mice.

Conclusions:

• This study is the first to demonstrate the effectiveness of IL-17-neutralizing antibody treatment in a cigarette smoke-induced COPD model.
• The antibody treatment successfully reversed established lung damage and inflammation, even when initiated after disease onset.
• IL-17-neutralizing antibodies represent a potential therapeutic strategy for managing COPD.