TECHNICAL ASPECTS OF EVALUATING CYTOKINE PROFILE AND LEUKOCYTE REACTION IN BILE DUCT OBTURATION OF DIFFERENT ORIGIN

The study was carried out to assess the prospects for the combined use of leukocyte and cytokine indices in the bile duct obstruction of different genesis.
We have performed a study of the patients with mechanical jaundice, either due to tumor (14 persons), or non-tumor genesis (16 persons). Concentrations of cytokines (IL-1, IL-4, IL-8, TNFα) were determined in blood serum before surgical intervention. The total activity of endogenous inflammatory mediators in the serum of patients was estimated as an index of inflammatory activity (IVA), which was calculated using the following formula: IVA = (IL-1 + TNFα)/IL-4. In addition, a number of leukocyte indices were calculated. The cellular component in the index estimation makes it possible to clarify the intensity of the inflammatory reaction, and to suggest the direction of the functional changes among the  immunocompetent cells.
It was shown that IVA in presence of malignancy is significantly higher than in benign conditions. Overactivation of immune response in tumors may be caused by a significant predominance of pro-nflammatory cytokines. Moreover, in cases of malignant tumor growth, both with or without cholangitis, the index scores of humoral and cellular components let us suggest the some problems with regeneration, due to pro-inflammatory domination of immune response, which does not ensure activation of the corresponding reactions. It has been established that the leukocyte intoxication index (LII) is increased,in patients with a combination of malignant disorder and cholangitis, and the immunoreactivity index (MDI) is lowered. In absence of cholangitis, the opposite pattern is observed, when LII is slightly lowered and MDI is elevated. Correlation analysis for the patients with cholangitis revealed a high association of cytokine imbalance and endogenous intoxication. A complex of cytokine and leukocyte indices is promising, when each of them reflects a certain part of the process, and their combination gives an integral picture of the pathology and allows to predict development of the disease. Such an approach, seems to increase the diagnostic significance of these immunological indices, primarily, the cytokine production, and may be used when predicting currence of complications in the surgical treatment of the disease.

1. Бережная Н.М. Цитокиновая регуляция при патологии: стремительное развитие и неизбежные вопросы // Цитокины и воспаление, 2007. Т. 6, № 2. С. 26-34. [Berezhnaya N.M. Cytokine network regulation in pathology: rapid progress in knowledge and inevitable questions. Tsitokiny i vospalenie = Cytokine and Inflammation, 2007, Vol. 6, no. 2, pp. 26-34. (In Russ.)]

2. Гаджиев Дж.Н., Тагиев Э.Г., Гаджиев Н.Дж. Состояние цитокинового статуса у больных с механической желтухой доброкачественного генеза // Хирургия. Журнал им. Н.И. Пирогова, 2015. № 5. С.56-58. [Gadzhiev Dzh.N., Tagiev Е.G., Gadzhiev N.Dzh. The state of cytokine status in patients with mechanical jaundice of benign origin. Khirurgiya. Zhurnal im. N.I. Pirogova. = N. Pirogov Surgery Journal, 2015, Vol. 5, pp. 56-58. (In Russ.)]

3. Гаркави Л.Х., Квакина Е.Б., Уколова М.А. Адаптационные реакции и резистентность организма. Ростов-на-Дону, 1990. 224 с. [Garkavi L.H., Kvakina E.B., Ukolova M.A. Adaptive response and resistance of organism]. Rostov-on-Don, 1990. 224 p.

4. Кальф-Калиф Я.Я. О лейкоцитарном индексе и его практическом значении // Врачебное дело, 1941. № 1. С. 31-35. [Kalf-Kalif Ya.Ya. About the leukocyte index and its practical value. Vrachebnoye delo = Medical Practice, 1941, Vol. 1, pp. 31-35. (In Russ.)]

5. Карабанов Г.Н. Использование лейкоцитарной формулы крови для оценки тяжести интоксикации // Вестник хирургии им. И.И. Грекова, 1989. № 4. С. 146-149. [Karabanov G.N. The using of blood leukocyte to assess the severity of intoxication. Vestnik khirurgii im. I.I. Grekova = I. Grekov Surgery Bulletin, 1989, Vol. 4, pp. 146-149. (In Russ.)]

6. Карпунина Н.С., Бахметьев Б.А., Заикина М.В. Признаки микробной сенсибилизации у больных с различными сердечно-сосудистыми заболеваниями // Журнал микробиологии, эпидемиологии и иммунобиологии, 2015. № 1. С. 75-81. [Karpunina N.S., Bakhmetiev B.A., Zaikina M.V. Signs of microbial sensibilization in patients with various cardiovascular diseases. Zhurnal mikrobiologii, epidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology, 2015, Vol. 1, pp. 75-81. (In Russ.)]

7. Касимов Э.М., Заргарли И.А., Намазова И.К., Меджидова С.Р. Сравнительная оценка иммунологической реактивности при сочетанной травме глаза // Офтальмология, 2011. Т. 3, №. 7. С. 50-55. [Kasimov E.M., Zargali I.A., Namazova I.K., Medzhidova S.R. Comparison of immunological reactivity in associated eye trauma. ftalmologiya = Ophthalmology, 2011, Vol. 3, no. 7, pp. 50-55. (In Russ.)]

8. Кобец Т.В., Кобец Ю.В., Гавриков И.В. Применение современных информационных технологий для оценки эффективности лечения на курорте // Молодой ученый, 2016. № 5. С. 219-221. [Kobets T.V., Kobets Yu.V., Gavrikov I.V. Applying modern information technologies for the assessment of resort treatment efficiency. Molodoy uchenyy = Young Scientist, 2016, Vol. 5, pp. 219-221. (In Russ.)]

9. Кучеренко В.З. Применение методов статистического анализа для изучения общественного здоровья и здравоохранения. М.: ГЭОТАР-Медиа, 2007. 299 с. [Kucherenko V.Z. The applying of methods of statistical analysis for studying public health and healthcare]. Moscow: GEOTAR-Media, 2007. 299 p.

10. Останин А.А., Леплина О.Ю., Тихонова М.А., Шевела Е.Я., Курганова Е.В., Стрельцова Е.И., Черных Е.Р. Цитокинопосредованные механизмы развития системной иммуносупрессии у больных с гнойнохирургической патологией // Цитокины и воспаление, 2002. Т. 1, № 1. С. 38-45. [Ostanin A.A., Leplina O.Yu., Tikhonova M.A., Shevela E.Ya., Kurganova E.V., Streltsova E.I., Chernykh E.R. Cytokine-mediated mechanisms of systemic immune suppression in patients with surgical infections. Tsitokiny i vospalenie = Cytokine and Inflammation, 2002, Vol. 1, no. 1, pp. 38-45. (In Russ.)]

11. Островский В. К., Мащенко А. В., Янголенко Д. В., Макаров С. В. Показатели крови и лейкоцитарного индекса интоксикации в оценке тяжести и определении прогноза при воспалительных, гнойных и гнойнодеструктивных заболеваниях // Клиническая лабораторная диагностика, 2006. № 6. С. 50-53. [Ostrovsky V.К., Mashchenko А.V., Yangolenko D.V., Макаrov S.V. The parameters of blood and leukocytic intoxication index in the evaluation of the severity of inflammatoгу, purulent, and pyodestructive diseases. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics, 2006, Vol. 6, pp. 50-53. (In Russ.)]

12. Островский В.К., Мащенко А.В., Макаров С.В. Оценка тяжести и прогноз гнойнодеструктивных заболеваний органов брюшной полости // Хирургия. Журнал им. Н.И. Пирогова, 2007. № 1. С. 33-37. [Ostrovsky V.K., Mashchenko A.V., Makarov S.V. Assessment of severity assessment and prognosis of pyodestructive abdominal diseases. Khirurgiya. Zhurnal im. N.I. Pirogova. = N. Pirogov Surgery Journal, 2007, Vol. 1, pp. 33-37. (In Russ.)]

13. Пахрова О.А., Криштоп В.В., Курчанинова М.Г., Румянцева Т.А. Лейкоцитарные показатели крови при адаптации к острой экспериментальной гипоксии головного мозга в зависимости от уровня стрессоустойчивости // Современные проблемы науки и образования, 2016. № 6. С. 231. [Pakhrova O.A., Krishtop V.V., Kurchaninova M.G., Rumyantseva T.A. Changes of blood leukocyte indices under acute experimental cerebral hypoxia in rats with different levels of stress resistance. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education, 2016, Vol. 6, p. 231. (In Russ.)]

14. Плеханов А.Н., Чикотеев С.П., Товаршинов А.И. Изменение уровней цитокинов в крови при развитии печеночной недостаточности после операций на печени // Медицинская иммунология, 2006. Т. 8, № 1. С. 61-66. [Plekhanov A.N., Chikoteev S.P., Tovarshinov F.I., Soboleva N.I. Changes of blood cytokine levels in the course of developing liver insufficiency after hepatic surgery. Meditsinskaya immunologiya = Medical Immunology (Russia), 2006, Vol. 8, no. 1, pp. 61-66. [In Russ.)] doi: 10.15789/1563-0625-2006-1-61-66.

15. Сарап П.В., Тутынин К.В., Булыгин Г.В., Камзалакова Н.И., Швецкий А.Г., Степаненко А.В. Метод прогнозирования и выявления осложнений в раннем послеоперационном периоде. Патент на изобретение № 2190216, 2001. [Sarap P.V., Tutynin K.V., Bulygin G.V., Kamzalakova N.I., Shvetsky A.G., Stepanenko A.V. Method of prediction and rejection of complications in the early postoperative period]. Patent No. 2190216, 2001.

16. Симбирцев А.С. Цитокины – новая система регуляции защитных реакций организма // Цитокины и воспаление, 2002. Т. 1, № 1. С. 9-16. [Simbirtsev A.S. Cytokines as a new system, regulating body defense reactions. Tsitokiny i vospalenie = Cytokine and Inflammation, 2002, Vol. 1, no. 1, pp. 9-16. (In Russ.)]

17. Тагиев Э.Г. Динамика интерлейкина 4 при хирургическом лечении механической желтухи доброкачественного генеза // Здравоохранение (Минск), 2016. № 5. С. 4-8. [Tagiev E.G. Interleukin-4 dynamics in patients with benign obstructive jaundice surgical management. Zdravookhranenie (Minsk) = Public Health (Minsk), 2016, Vol. 5, pp. 4-8. (In Russ.)]

18. Cortvrindt C., Speeckaert R., Moerman A., Delanghe J.R., Speeckaert M.M. The role of interleukin-17A in the pathogenesis of kidney diseases. Pathology, 2017, Vol. 49, no. 3, pp. 247-258.

19. Kudo M. Immuno-oncology in hepatocellular carcinoma: 2017 update. Oncology, 2017, Vol. 93, Suppl. 1, pp. 147-159.

20. Marra F., Tacke F. Roles for chemokines in liver disease. Gastroenterology, 2014, Vol. 147, pp. 577-594.

21. Shao Y.Y., Lin H., Li Y.S., Lee Y.H., Chen H.M., Cheng A.L., Hsu C.H. High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma. Jpn. J. Clin. Oncol., 2017, Vol. 47, no. 10, pp. 949-953.

22. Wasmuth H.E., Tacke F., Trautwein C. Chemokines in liver inflammation and fibrosis. Semin. Liver. Dis., 2010, Vol. 30, pp. 215-225.

23. Xu C., Qiao Y., Zhang D. Expression of Toll-like receptors in human hepatocellular carcinoma and its correlation with inflammasome-associated cytokines. Chinese journal of cellular and molecular immunology. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2017, Vol. 33, no. 9, pp. 1182-1186.

24. Yao Y., Xie S., Yang C., Zhang J., Wu X., Sun H. Biomarkers in the evaluation and management of chronic rhinosinusitis with nasal polyposis. Eur. Arch. Otorhinolaryngol., 2017, Vol. 274, no. 10, pp. 3559-3566.