Erythromycin Prevents Elastin Peptide-Induced Emphysema and Modulates CD4+T Cell Responses in Mice

Shudan Tang,* Tingting Ma,* Hui Zhang,* Jianquan Zhang, Xiaoning Zhong, Caimei Tan, Ye Qiu, Wen Zeng, Xin Feng Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianquan ZhangDepartment of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Qingxiu, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 771 535 1176Email jqzhang2002@126.comPurpose: Elastin peptides (EP) can induce lung inflammation and emphysema. Erythromycin has been shown to decrease acute exacerbation frequency and delay lung function decline in chronic obstructive pulmonary disease patients and ameliorate emphysema in murine models; however, the mechanism remains unclear. We aimed to observe the preventive and immunomodulatory effects of erythromycin in a mouse model of EP-induced emphysema.Methods: In the in vivo study, Balb/c mice were treated with EP intranasally on day 0, and then administered erythromycin (100 mg/kg) or vehicle orally on day 1, which was continued every other day. Mice exposed to cigarette smoke were used as an emphysema positive control. The severity of emphysema and inflammation in the lungs of EP-exposed mice with or without erythromycin treatment were observed on day 40 after EP administration. In the in vitro study, naïve CD4+T cells were isolated from healthy mice spleens and stimulated by EP with or without erythromycin incubation. Flow cytometry was used to measure the proportions of Th1, Th17, and Treg cells. ELISA was used to detect cytokine levels of IFN-γ, IL-17, IL-6, and TGF-β. Transcript levels of Ifnγ, IL17a, and Foxp3 were evaluated by qRT-PCR.Results: After exposure to EP, Th1 and Th17 cell percentages and the levels of inflammatory cytokines increased in vivo and in vitro, while Treg cells decreased in vivo. Erythromycin reduced IFN-γ, IL-17, IL-6 inflammatory cytokines, MLI, and the inflammation score in the lungs of EP-exposed mice. In vitro, erythromycin also limited Th17 and Th1 cell differentiation and downregulated transcript levels of Ifnγ and IL17a in the EP-stimulated CD4+T cells.Conclusion: The Th1 and Th17 cell responses were increased in EP-induced emphysema. Prophylactic use of erythromycin effectively ameliorated emphysema and modulated CD4+T cells responses in EP-induced lung inflammation in mice.Keywords: Th1, Th17, Treg cells, inflammation, lungs