The Immunomodulatory Effects of Spleen Aminopeptide on Connective Tissue Disease-Related Interstilial Lung Disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

The First Affiliated Hosptital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong, 510120, China;

Corresponding author：

Keywords：

Connective tissue disease-related interstitial lung disease; Spleen aminopeptid; Human cytomegalovirus; Immunomodulation

DOI：

10.7507/1671-6205.2016053

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Objective To explore the therapeutic effects of spleen aminopeptide on connective tissue disease-related interstitial lung disease (CTD-ILD) and its mechanism for anti-fibrosis. Methods Ninety patients with CTD-ILD admitted between February 2014 and May 2015 were recruited in the study. The CTD-ILD patients were randomly divided into group A (conventional therapy alone) and group B (conventional therapy plus spleen aminopeptide). Peripheral blood collected from CTD-ILD patients were subjected to performance of flow cytometric analysis and cytokine/chemokines profiling by liquid Chip and ELISA assay. Pulmonary function test and high resolution CT (HRCT) scan were performed before and after the treatments for 12 weeks. Human cytomegalovirus (HCMV) DNA in the patients' blood was tested by Q-PCR. Results Significantly improved lung function and HRCT score were observed in group B, but not in group A. The levels of Treg and IFN-γ were significantly increased in group B, compared with those in group A where markedly increased IL-6, IL-10 and IL-17 were detected (P < 0.05). There was higher virus negative reversal rate in group B than that in group A (P < 0.05). Conclusion Spleen aminopeptid can effectively regulate deregulated immune microenvironment in CTD-ILD patients and inhibit HCMV replication, thereby block pulmonary fibrotic development.

Citation： Wu Caiyun, Luo Qun, Wang Wei, Wang Yansheng, Chen Qiang, Yu Baodan, Liu Ming, Zhang Huanhuan, Zheng Lixia, Xu Jun. The Immunomodulatory Effects of Spleen Aminopeptide on Connective Tissue Disease-Related Interstilial Lung Disease. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(3): 222-226. doi: 10.7507/1671-6205.2016053 Copy

1.	卞大晨, 肖永龙, 刘布俊, 等.结缔组织疾病相关性间质性肺病与特发性间质性肺炎比较研究.中国呼吸与危重监护杂志, 2014, 13:263-267.
2.	Bresser P, Jansen HM, Weller FR, et al. T-cell activation in the lungs of patients with systemic sclerosis and its relation with pulmonary fibrosis. Chest, 2001, 120:66S-68S.
3.	Papakosta D, Manika K, Gounari E, et al. Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like cells in cryptogenic organizing pneumonia. Respirology, 2014, 19:748-754.
4.	Kotsianidis I, Nakou E, Bouchliou I, et al. Global impairment of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2009, 179:1121-1130.
5.	Dunn HS, Haney DJ, Ghanekar SA, et al. Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors. J Infect Dis, 2002, 186:15-22.
6.	Tang YW, Johnson JE, Browning PJ, et al. Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis. J Clin Microbiol, 2003, 41:2633-2640.
7.	Yonemaru M, Kasuga I, Kusumoto H, et al. Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis. Eur Respir J, 1997, 10:2040-2045.
8.	赖金梅, 黄旺, 苏玉琴, 等.脾氨肽口服冻干粉对慢性阻塞性肺疾病的疗效观察.医药前沿, 2012:232-233.
9.	何志红, 郑颖, 金颖, 等.脾氨肽对支气管哮喘相关细胞因子调控的研究.国际呼吸杂志, 2015, 35:165-168.
10.	American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med, 2002, 165:277-304.
11.	Goldin JG, Lynch DA, Strollo DC, et al. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest, 2008, 134:358-367.
12.	Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol, 2012, 30:531-564.
13.	Costantino CM, Baecher-Allan CM, Hafler DA. Human regulatory T cells and autoimmunity. Eur J Immunol, 2008, 38:921-924.
14.	O'Reilly S, Ciechomska M, Cant R, et al. Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein. J Biol Chem, 2014, 289:9952-9960.
15.	Vittal R, Fan L, Greenspan DS, et al. IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis. Am J Physiol Lung Cell Mol Physiol, 2013, 304:L401-L414.
16.	Giannopoulou M, Iszkula SC, Dai C, et al. Distinctive role of Stat3 and Erk-1/2 activation in mediating interferon-γ inhibition of TGF-β1 action. Am J Physiol Renal Physiol, 2006, 290:F1234-F1240.

1. 卞大晨, 肖永龙, 刘布俊, 等.结缔组织疾病相关性间质性肺病与特发性间质性肺炎比较研究.中国呼吸与危重监护杂志, 2014, 13:263-267.
2. Bresser P, Jansen HM, Weller FR, et al. T-cell activation in the lungs of patients with systemic sclerosis and its relation with pulmonary fibrosis. Chest, 2001, 120:66S-68S.
3. Papakosta D, Manika K, Gounari E, et al. Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like cells in cryptogenic organizing pneumonia. Respirology, 2014, 19:748-754.
4. Kotsianidis I, Nakou E, Bouchliou I, et al. Global impairment of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2009, 179:1121-1130.
5. Dunn HS, Haney DJ, Ghanekar SA, et al. Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors. J Infect Dis, 2002, 186:15-22.
6. Tang YW, Johnson JE, Browning PJ, et al. Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis. J Clin Microbiol, 2003, 41:2633-2640.
7. Yonemaru M, Kasuga I, Kusumoto H, et al. Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis. Eur Respir J, 1997, 10:2040-2045.
8. 赖金梅, 黄旺, 苏玉琴, 等.脾氨肽口服冻干粉对慢性阻塞性肺疾病的疗效观察.医药前沿, 2012:232-233.
9. 何志红, 郑颖, 金颖, 等.脾氨肽对支气管哮喘相关细胞因子调控的研究.国际呼吸杂志, 2015, 35:165-168.
10. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med, 2002, 165:277-304.
11. Goldin JG, Lynch DA, Strollo DC, et al. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest, 2008, 134:358-367.
12. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol, 2012, 30:531-564.
13. Costantino CM, Baecher-Allan CM, Hafler DA. Human regulatory T cells and autoimmunity. Eur J Immunol, 2008, 38:921-924.
14. O'Reilly S, Ciechomska M, Cant R, et al. Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein. J Biol Chem, 2014, 289:9952-9960.
15. Vittal R, Fan L, Greenspan DS, et al. IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis. Am J Physiol Lung Cell Mol Physiol, 2013, 304:L401-L414.
16. Giannopoulou M, Iszkula SC, Dai C, et al. Distinctive role of Stat3 and Erk-1/2 activation in mediating interferon-γ inhibition of TGF-β1 action. Am J Physiol Renal Physiol, 2006, 290:F1234-F1240.

Chinese Journal of Respiratory and Critical Care Medicine

The Immunomodulatory Effects of Spleen Aminopeptide on Connective Tissue Disease-Related Interstilial Lung Disease

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