mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2016-6-537-544mimmun-1134Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESХАРАКТЕРИСТИКА ПРОФИЛЯ ПРОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ У БОЛЬНЫХ С РАЗЛИЧНЫМИ ФЕНОТИПАМИ АЛЬФА-1-АНТИТРИПСИНАPROINFLAMMATORY CYTOKINE PROFILE IN PATIENTS WITH DIFFERENT ALPHA-1-ANTITRYPSIN PHENOTYPESПерваковаМ. Ю.PervakovaM. Yu.

врач клинической лабораторной диагностики лаборатории диагностики аутоиммунных заболеваний НМЦ по молекулярной медицине 

Laboratory Doctor, Diagnostic Laboratory for Autoimmune Disorders, Research Center of Molecular Medicine

margaritalerner@gmail.comЛапинС. В.LapinS. V.

к.м.н., старший научный сотрудник, заведующий лабораторией диагностики аутоиммунных заболеваний НМЦ по молекулярной медицине

PhD (Medicine), Senior Research Associate, Head, Laboratory for Diagnostics of Autoimmune Diseases, Research Center of Molecular Medicine

margaritalerner@gmail.comСурковаЕ. А.SurkovaE. A.

к.б.н., старший научный сотрудник лаборатории диагностики аутоиммунных заболеваний НМЦ по молекулярной медицине

PhD (Biology), Senior Research Associate, Laboratory for Diagnostics of Autoimmune Diseases, Research Center of Molecular Medicine

margaritalerner@gmail.comТкаченкоО. Ю.TkachenkoO. Yu.

лаборант, лаборатория диагностики аутоиммунных заболеваний НМЦ по молекулярной медицине

Laboratory Assistant, Laboratory for Diagnostics of Autoimmune Diseases, Research Center of Molecular Medicine

margaritalerner@gmail.comБудковаА. И.BudkovaA. I.

студент

Student,

margaritalerner@gmail.comГусеваВ. И.GusevaV. I.

лаборант, лаборатория диагностики аутоиммунных заболеваний НМЦ по молекулярной медицине

Laboratory Assistant, Laboratory for Diagnostics of Autoimmune Diseases, Research Center of Molecular Medicine

margaritalerner@gmail.comТитоваО. Н.TitovaO. N.

д.м.н., профессор, директор НИИ пульмонологии Г

PhD, MD (Medicine), Professor, Director, Research Institute of Pulmonology

margaritalerner@gmail.comЭмануэльВ. Л.EmanuelV. L.

 

д.м.н., профессор, заведующий кафедрой клинической лабораторной диагностики с курсом молекулярной медицины

PhD, MD (Medicine), Professor, Head, Department of Clinical Laboratory Diagnostics with a Course of Molecular Medicine

margaritalerner@gmail.comТотолянАрег А.TotolianAreg A.

д.м.н., член-корр. РАН, профессор, директор Санкт-Петербургского научно-исследовательского института эпидемиологии и микробиологии им. Пастера

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Director

margaritalerner@gmail.comГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ, Санкт-Петербург, РоссияРоссияThe First St. Petersburg I. Pavlov State Medical University, St. Petersburg, Russian FederationRussian FederationГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ, Санкт-Петербург, Россия Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии им. Пастера, Санкт-Петербург, РоссияРоссияThe First St. Petersburg I. Pavlov State Medical University, St. Petersburg, Russian Federation St. Petersburg Pasteur Institute, St. Petersburg, Russian FederationRussian Federation201607122016186537544Copyright © Первакова М.Ю., Лапин С.В., Суркова Е.А., Ткаченко О.Ю., Будкова А.И., Гусева В.И., Титова О.Н., Эмануэль В.Л., Тотолян А., 20162016Первакова М.Ю., Лапин С.В., Суркова Е.А., Ткаченко О.Ю., Будкова А.И., Гусева В.И., Титова О.Н., Эмануэль В.Л., Тотолян А.Pervakova M.Y., Lapin S.V., Surkova E.A., Tkachenko O.Y., Budkova A.I., Guseva V.I., Titova O.N., Emanuel V.L., Totolian A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1134

Альфа-1-антитрипсин (А1АТ) обладает широким спектром защитных эффектов, направленных на уменьшение вторичного повреждения при воспалении. Помимо ингибирования сериновых протеаз, А1АТ осуществляет регуляцию продукции провоспалительных цитокинов. Известно большое количество фенотипических вариантов А1АТ, которые могут изменять цитокиновый профиль при воспалительном процессе и повышать риск ассоциированных с дефицитом А1АТ заболеваний.

Целью нашего исследования являлась оценка цитокинового профиля у больных с различными фенотипами А1АТ.

Было собрано 86 образцов сыворотки крови больных с подозрением на дефицит А1АТ, в которых были определены фенотипы и концентрации А1АТ. В зависимости от фенотипа образцы были разделены на четыре группы: с PiMM, PiZZ, PiMZ и редкими фенотипами А1АТ. В этих группах были измерены уровни IFNγ, TNFα, IL-6, IL-8 и IL-17 методом иммуноферментного анализа с помощью коммерческих тест-систем производства ООО «Цитокин» (Россия).

Уровень IL-6 оказался повышен в группе с PiZZ-фенотипом и составил 73,52±4,363 pg/ml, тогда как при PiMM-фенотипе среднее значение IL-6 было 45,61±8,012 pg/ml, p < 0,05. Также в группах с PiZZ- и PiMZ-фенотипами было обнаружено повышение IL-17 по сравнению с PiMM-фенотипом (p < 0,001). Средние значения IL-17 у больных с PiZZ-, PiMZ- и PiMM-фенотипами составили 80,13±13,56 pg/ml, 106,7±26,28 pg/ml и 42,73±18,52 pg/ml соответственно. При этом уровни IL-8, IFNγ и TNFα не отличались при различных фенотипах А1АТ. Результаты нашего исследования позволяют сделать заключение, что дисбаланс цитокинов может играть важную роль в возникновении ассоциированных с дефицитом А1АТ заболеваний.

 

Alpha-1-antitrypsin (A1AT) exerts a wide spectrum of protective effects, being focused on reduction of secondary injury in inflammation. Moreover, A1AT inhibits some serine proteases, and down-regulates production of proinflammatory cytokines. A number of known A1AT phenotypes is accompanied by affection of cytokine profile in inflammatory processes, thus increasing the risk of disorders associated with A1AT deficiency.

The aim of our study was to evaluate cytokine profiles in the patients with different A1AT phenotypes. Were collected eighty-six blood sera from the persons with suspected A1AT deficiency. The A1AT phenotypes

and concentrations were determined in these samples. The patients were divided into four groups, depending on their A1AT variants, i.e., PiMM, PiZZ, PiMZ and rare A1AT phenotypes. The serum levels of IFNγ, TNFα, IL-6, IL-8, and IL-17 were measured in these groups by means of ELISA technique.

The mean levels of IL-6 comprised 73.52±4.363 pg/ml in the patients with PiZZ phenotype, being higher than in cases of PiMM phenotype (45.61±8.01 pg/ml, p < 0.05). The IL-17 levels were also found to be increased in the groups with PiZZ and PiMZ phenotypes, as compared with PiMM phenotype (p < 0.001). The mean IL-17 values in the samples with PiZZ, PiMZ, and PiMM phenotypes were 80.13±13.56 pg/ml, 106.7±26.28 pg/ml and 42.73±18.52 pg/ml, respectively. Meanwhile, there were no significant differences in IL-8, IFNγ and TNFα levels among different A1AT phenotypes.

The results of this study let us conclude that the cytokine imbalance may be crucial to onset of diseases associated with A1AT deficiency.

воспалениеальфа-1-антитрипсинцитокинфенотип альфа-1-антитрипсинадефицит альфа-1-антитрипсинаinflammationalpha-1-antitrypsincytokinealpha-1-antitrypsin phenotypealpha-1-antitrypsin deficiencyReferencesШевченко О.П. Белки острой фазы воспаления. Лаборатория, 1996, № 1. С. 10-17. [Shevchenko O.P. Acute phase proteins. Laboratoriya = Laboratory, 1996, no. 1, pp. 10-17. (In Russ.])Шевченко О.П. Белки острой фазы воспаления. Лаборатория, 1996, № 1. С. 10-17. [Shevchenko O.P. Acute phase proteins. Laboratoriya = Laboratory, 1996, no. 1, pp. 10-17. (In Russ.])Stoller J.K., Lacbawan F.L., Aboussouan L.S. Alpha-1 antitrypsin deficiency. Gene reviews, 2006.Stoller J.K., Lacbawan F.L., Aboussouan L.S. Alpha-1 antitrypsin deficiency. Gene reviews, 2006.Lockett A.D., van Demark M., Gu Y., Schweitzer K.S., Sigua N., Kamocki K., Fijalkowska I., Garrison J., Fisher A.J., Serban K., Wise R.A., Flotte T.R., Mueller C., Presson R.G.Jr., Petrache H.I., Tuder R.M., Petrache I. Effect of cigarette smoke exposure and structural modifications on the alpha-1 Antitrypsin interaction with caspases. Mol. Med., 2012, Vol. 18, pp. 445-454.Lockett A.D., van Demark M., Gu Y., Schweitzer K.S., Sigua N., Kamocki K., Fijalkowska I., Garrison J., Fisher A.J., Serban K., Wise R.A., Flotte T.R., Mueller C., Presson R.G.Jr., Petrache H.I., Tuder R.M., Petrache I. Effect of cigarette smoke exposure and structural modifications on the alpha-1 Antitrypsin interaction with caspases. Mol. Med., 2012, Vol. 18, pp. 445-454.Feng Y., Xu J., Zhou Q., Wang R., Liu N., Wu Y., Yuan H., Che H. Alpha-1 Antitrypsin prevents the development of preeclampsia through suppression of oxidative stress. Front Physiol., 2016, Vol. 7, p. 176.Feng Y., Xu J., Zhou Q., Wang R., Liu N., Wu Y., Yuan H., Che H. Alpha-1 Antitrypsin prevents the development of preeclampsia through suppression of oxidative stress. Front Physiol., 2016, Vol. 7, p. 176.Stockley R.A. The multiple facets of alpha-1-antitrypsin. Ann. Transl. Med., 2015, Vol. 3, no. 10, p. 130.Stockley R.A. The multiple facets of alpha-1-antitrypsin. Ann. Transl. Med., 2015, Vol. 3, no. 10, p. 130.Zampronio A.R., Soares D.M., Souza G.E. Central mediators involved in the febrile response: effects of antipyretic drugs. Temperature (Austin), 2015, Vol. 2, no. 4, pp. 506-521.Zampronio A.R., Soares D.M., Souza G.E. Central mediators involved in the febrile response: effects of antipyretic drugs. Temperature (Austin), 2015, Vol. 2, no. 4, pp. 506-521.Koo J.B., Han J.S. Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells. J. Toxicol. Sci., 2016, Vol. 41, no. 1, pp. 77-89.Koo J.B., Han J.S. Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells. J. Toxicol. Sci., 2016, Vol. 41, no. 1, pp. 77-89.de Carvalho F.O., Felipe F.A., de Melo Costa A.C., Teixeira L.G., Silva É.R., Nunes P.S., Shanmugam S., de Lucca Junior W., Quintans J.S., de Souza Araújo A.A. Inflammatory mediators and oxidative stress in animals subjected to smoke inhalation: a systematic review. Lung, 2016.de Carvalho F.O., Felipe F.A., de Melo Costa A.C., Teixeira L.G., Silva É.R., Nunes P.S., Shanmugam S., de Lucca Junior W., Quintans J.S., de Souza Araújo A.A. Inflammatory mediators and oxidative stress in animals subjected to smoke inhalation: a systematic review. Lung, 2016.Ansarin K., Rashidi F., Namdar H., Ghaffari M., Sharifi A. Echocardiographic evaluation of the relationship between inflammatory factors (IL6, TNFalpha, hs-CRP) and secondary pulmonary hypertension in patients with COPD. A Cross Sectional Study. Pneumologia, 2015, Vol. 64, no. 3, pp. 31-35.Ansarin K., Rashidi F., Namdar H., Ghaffari M., Sharifi A. Echocardiographic evaluation of the relationship between inflammatory factors (IL6, TNFalpha, hs-CRP) and secondary pulmonary hypertension in patients with COPD. A Cross Sectional Study. Pneumologia, 2015, Vol. 64, no. 3, pp. 31-35.Chen Z., Shao X., Dou X., Zhang X., Wang Y., Zhu C., Hao C., Fan M., Ji W., Yan Y. Role of the mycoplasma pneumoniae/interleukin-8/neutrophil axis in the pathogenesis of pneumonia. PLoS One, 2016, Vol. 11, no. 1, p. e0146377.Chen Z., Shao X., Dou X., Zhang X., Wang Y., Zhu C., Hao C., Fan M., Ji W., Yan Y. Role of the mycoplasma pneumoniae/interleukin-8/neutrophil axis in the pathogenesis of pneumonia. PLoS One, 2016, Vol. 11, no. 1, p. e0146377.Majak P. Tumor necrosis factor alpha as an asthma biomarker in early childhood. Pneumonol. Alergol. Pol., 2016, Vol. 84, no. 3, pp. 143-144.Majak P. Tumor necrosis factor alpha as an asthma biomarker in early childhood. Pneumonol. Alergol. Pol., 2016, Vol. 84, no. 3, pp. 143-144.Cosmi L., Liotta F., Annunziato F. Th17 regulating lower airway disease. Curr Opin Allergy Clin. Immunol., 2016, Vol. 16, no. 1, pp. 1-6.Cosmi L., Liotta F., Annunziato F. Th17 regulating lower airway disease. Curr Opin Allergy Clin. Immunol., 2016, Vol. 16, no. 1, pp. 1-6.Miossec P., Korn T., Kuchroo V.K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med., 2009, Vol. 361, no. 9, pp. 888-898.Miossec P., Korn T., Kuchroo V.K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med., 2009, Vol. 361, no. 9, pp. 888-898.Ortiz G, Salica J.P., Chuluyan E.H., Gallo J.E. Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option? Biol. Res., 2014, Vol. 47, p. 58.Ortiz G, Salica J.P., Chuluyan E.H., Gallo J.E. Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option? Biol. Res., 2014, Vol. 47, p. 58.Lewis E.C., Shapiro L., Bowers O.J., Dinarello C.A. Alpha1-antitrypsin monotherapy prolongs islet allograſt survival in mice. Proc. Natl. Acad. Sci. USA, 2005, Vol. 102, no. 34, pp. 12153-12158.Lewis E.C., Shapiro L., Bowers O.J., Dinarello C.A. Alpha1-antitrypsin monotherapy prolongs islet allograſt survival in mice. Proc. Natl. Acad. Sci. USA, 2005, Vol. 102, no. 34, pp. 12153-12158.Subramaniyam D., Virtala R., Pawłowski K., Clausen I.G., Warkentin S., Stevens T., Janciauskiene S. TNF-alpha-induced self expression in human lung endothelial cells is inhibited by native and oxidized alpha1-antitrypsin. Int. J. Biochem. Cell Biol., 2008, Vol. 40, no. 2, pp. 258-271.Subramaniyam D., Virtala R., Pawłowski K., Clausen I.G., Warkentin S., Stevens T., Janciauskiene S. TNF-alpha-induced self expression in human lung endothelial cells is inhibited by native and oxidized alpha1-antitrypsin. Int. J. Biochem. Cell Biol., 2008, Vol. 40, no. 2, pp. 258-271.Bergin D.A., Reeves E.P., Hurley K., Wolfe R., Jameel R., Fitzgerald S., McElvaney N.G. The circulating proteinase inhibitor alpha-1 antitrypsin regulates neutrophil degranulation and autoimmunity. Sci. Transl. Med., 2014, Vol. 6, no. 217, p. 217ra1.Bergin D.A., Reeves E.P., Hurley K., Wolfe R., Jameel R., Fitzgerald S., McElvaney N.G. The circulating proteinase inhibitor alpha-1 antitrypsin regulates neutrophil degranulation and autoimmunity. Sci. Transl. Med., 2014, Vol. 6, no. 217, p. 217ra1.Pott G.B., Chan E.D., Dinarello C.A., Shapiro L. Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood. J. Leukoc. Biol., 2009, Vol. 85, no. 5, pp. 886-895.Pott G.B., Chan E.D., Dinarello C.A., Shapiro L. Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood. J. Leukoc. Biol., 2009, Vol. 85, no. 5, pp. 886-895.Subramanian S., Shahaf G., Ozeri E., Miller L.M., Vandenbark A.A., Lewis E.C., Offner H. Sustained expression of circulating human alpha-1 antitrypsin reduces inflammation, increases CD4+FoxP3+ Treg cell population and prevents signs of experimental autoimmune encephalomyelitis in mice. Metab. Brain Dis., 2011, Vol. 26, no. 2, pp. 107-113.Subramanian S., Shahaf G., Ozeri E., Miller L.M., Vandenbark A.A., Lewis E.C., Offner H. Sustained expression of circulating human alpha-1 antitrypsin reduces inflammation, increases CD4+FoxP3+ Treg cell population and prevents signs of experimental autoimmune encephalomyelitis in mice. Metab. Brain Dis., 2011, Vol. 26, no. 2, pp. 107-113.Stone H., McNab G., Wood A.M., Stockley R.A., Sapey E. Variability of sputum inflammatory mediators in COPD and alpha1-antitrypsin deficiency. Eur. Respir. J., 2012, Vol. 40, no. 3, pp. 561-569.Stone H., McNab G., Wood A.M., Stockley R.A., Sapey E. Variability of sputum inflammatory mediators in COPD and alpha1-antitrypsin deficiency. Eur. Respir. J., 2012, Vol. 40, no. 3, pp. 561-569.Seixas S., Garcia O., Trovoada M.J., Santos M.T., Amorim A., Rocha J. Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism. Hum. Genet., 2001, Vol. 108, no. 1, pp. 20-30.Seixas S., Garcia O., Trovoada M.J., Santos M.T., Amorim A., Rocha J. Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism. Hum. Genet., 2001, Vol. 108, no. 1, pp. 20-30.Keren D.F. Protein electrophoresis in clinical diagnosis. Ed. A. London, 2003, pp. 71-77.Keren D.F. Protein electrophoresis in clinical diagnosis. Ed. A. London, 2003, pp. 71-77.Salahuddin P. Genetic variants of alpha1-antitrypsin. Curr. Protein Pept. Sci., 2010, Vol. 11, no. 2, pp. 101-117.Salahuddin P. Genetic variants of alpha1-antitrypsin. Curr. Protein Pept. Sci., 2010, Vol. 11, no. 2, pp. 101-117.Olfert I.M., Malek M.H., Eagan T.M., Wagner H., Wagner P.D. Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients ‘on’ or ‘off’ augmentation therapy. BMC Pulm. Med., 2014, Vol. 14, p. 106.Olfert I.M., Malek M.H., Eagan T.M., Wagner H., Wagner P.D. Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients ‘on’ or ‘off’ augmentation therapy. BMC Pulm. Med., 2014, Vol. 14, p. 106.Pervakova M.Yu., Emanuel V.L., Titova O.N., Lapin S.V., Mazurov V.I., Belyaeva I.B., Chudinov A.L., Blinova T.V., Surkova E.A. The diagnostic value of alpha-1-antitrypsin phenotype in Patients with granulomatosis with polyangiitis. International Journal of Rheumatology, 2016, pp. 1-5.Pervakova M.Yu., Emanuel V.L., Titova O.N., Lapin S.V., Mazurov V.I., Belyaeva I.B., Chudinov A.L., Blinova T.V., Surkova E.A. The diagnostic value of alpha-1-antitrypsin phenotype in Patients with granulomatosis with polyangiitis. International Journal of Rheumatology, 2016, pp. 1-5.Pervakova M.Y., Emanuel V.L., Surkova E.A., Mazing A.V., Lapin S.V., Kovaleva I.S., Sysoeva S.N. The comparison of techniques of electrophoresis, immune turbidynamic measurement and phenotyping of alpha-1-antitrypsin for diagnostic of alpha-1-antitrypsin insufficiency. Clin. Lab. Diagn., 2015, Vol. 10, pp. 28-32.Pervakova M.Y., Emanuel V.L., Surkova E.A., Mazing A.V., Lapin S.V., Kovaleva I.S., Sysoeva S.N. The comparison of techniques of electrophoresis, immune turbidynamic measurement and phenotyping of alpha-1-antitrypsin for diagnostic of alpha-1-antitrypsin insufficiency. Clin. Lab. Diagn., 2015, Vol. 10, pp. 28-32.Mahr A.D., Edberg J.C., Stone J.H., Hoffman G.S., St Clair E.W., Specks U., Dellaripa P.F., Seo P., Spiera R.F., Rouhani F.N., Brantly M.L., Merkel P.A. Alpha(1)-antitrypsin deficiency-related alleles Z and S and the risk of Wegener’s granulomatosis. Arthritis Rheum., 2010, Vol. 62, no. 12, pp. 3760-3767.Mahr A.D., Edberg J.C., Stone J.H., Hoffman G.S., St Clair E.W., Specks U., Dellaripa P.F., Seo P., Spiera R.F., Rouhani F.N., Brantly M.L., Merkel P.A. Alpha(1)-antitrypsin deficiency-related alleles Z and S and the risk of Wegener’s granulomatosis. Arthritis Rheum., 2010, Vol. 62, no. 12, pp. 3760-3767.American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am. J. Respir. Crit. Care Med., 2003, Vol. 168, no. 7, pp. 818-900.American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am. J. Respir. Crit. Care Med., 2003, Vol. 168, no. 7, pp. 818-900.Duan M.C., Zhang J.Q., Liang Y., Liu G.N., Xiao J., Tang H.J., Liang Y. Infiltration of IL-17-producing T cells and Treg cells in a mouse model of smoke-induced emphysema. Inflammation, 2016.Duan M.C., Zhang J.Q., Liang Y., Liu G.N., Xiao J., Tang H.J., Liang Y. Infiltration of IL-17-producing T cells and Treg cells in a mouse model of smoke-induced emphysema. Inflammation, 2016.Singh D. Chronic Obstructive Pulmonary Disease, Neutrophils and Bacterial Infection: A complex web involving IL-17 and IL-22 unravels. EBioMedicine, 2015, Vol. 2, no. 11, pp. 1580-1581.Singh D. Chronic Obstructive Pulmonary Disease, Neutrophils and Bacterial Infection: A complex web involving IL-17 and IL-22 unravels. EBioMedicine, 2015, Vol. 2, no. 11, pp. 1580-1581.Chen Q.R., Wang L.F., Xia S.S., Zhang Y.M., Xu J.N., Li H., Ding Y.Z. Role of interleukin-17A in early graſt rejection aſter orthotopic lung transplantation in mice. J. Thorac. Dis., 2016, Vol. 8, no. 6, pp. 1069-1079.Chen Q.R., Wang L.F., Xia S.S., Zhang Y.M., Xu J.N., Li H., Ding Y.Z. Role of interleukin-17A in early graſt rejection aſter orthotopic lung transplantation in mice. J. Thorac. Dis., 2016, Vol. 8, no. 6, pp. 1069-1079.Bergin D.A., Reeves E.P., Meleady P., Henry M., McElvaney O.J., Carroll T.P., Condron C., Chotirmall S.H., Clynes M., O’Neill S.J., McElvaney N.G. Alpha-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin. Invest., 2010, Vol. 120, no. 12, pp. 4236-4250.Bergin D.A., Reeves E.P., Meleady P., Henry M., McElvaney O.J., Carroll T.P., Condron C., Chotirmall S.H., Clynes M., O’Neill S.J., McElvaney N.G. Alpha-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin. Invest., 2010, Vol. 120, no. 12, pp. 4236-4250.Aldonyte R., Eriksson S., Piitulainen E., Wallmark A., Janciauskiene S. Analysis of systemic biomarkers in COPD patients. COPD, 2004, Vol. 1, no. 2, pp. 155-164.Aldonyte R., Eriksson S., Piitulainen E., Wallmark A., Janciauskiene S. Analysis of systemic biomarkers in COPD patients. COPD, 2004, Vol. 1, no. 2, pp. 155-164.Honda K., Wada H., Nakamura M., Nakamoto K., Inui T., Sada M., Koide T., Takata S., Yokoyama T., Saraya T., Kurai D., Ishii H., Goto H., Takizawa H. IL-17A synergistically stimulates TNF-alpha-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. Exp. Lung. Res., 2016, Vol. 42, no. 4, pp. 205-216.Honda K., Wada H., Nakamura M., Nakamoto K., Inui T., Sada M., Koide T., Takata S., Yokoyama T., Saraya T., Kurai D., Ishii H., Goto H., Takizawa H. IL-17A synergistically stimulates TNF-alpha-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. Exp. Lung. Res., 2016, Vol. 42, no. 4, pp. 205-216.

The authors declare that there are no conflicts of interest present.