ЦИТОКИНПРОДУЦИРУЮЩИЙ ПОТЕНЦИАЛ КЛЕТОК КРОВИ И ЦИТОКИНЫ СЫВОРОТКИ БОЛЬНЫХ ХРОНИЧЕСКИМ АТРОФИЧЕСКИМ ГАСТРИТОМ

Резюме. Исследовали цитокинпродуцирующий потенциал клеток крови, оцениваемый по индексу влияния поликлональных активаторов, представляющему собой отношение уровня стимулированной поликлональными активаторами продукции цитокина к уровню его спонтанной продукции, а также концентрацию цитокинов в сыворотке крови больных хроническим атрофическим гастритом. Было выявлено, что у больных с дисплазией слизистой оболочки желудка повышены индексы влияния поликлональных активаторов на продукцию клетками крови TNFα, IL-1β, IL-6, IL-8 и IL- 10 и концентрация IL-8 и IL-18BP в сыворотке крови по сравнению с больными без дисплазии. Установлено, что пациенты с величинами индексов влияния поликлональных активаторов на продукцию клетками крови IL-6 не ниже 164 условных единиц и IL-8 не ниже 38 условных единиц должны быть отнесены к группе риска по развитию дисплазии эпителия слизистой оболочки желудка.

1. Абелев Г.И., Эрайзер Т.Л. На пути к пониманию природы рака // Биохимия. – 2008. – Т. 73, № 5. – С. 605-618. Abelev G.I., Erayzer T.L. Na puti k ponimaniyu prirody raka [On the path to understandig the nature of cancer]. Biokhimiya – Biochemistry, 2008, vol. 73, no. 5, pp. 605-618.

2. Павлович И.М., Голофеевский В.Ю., Калиновский В.П. Предопухолевый потенциал хронического атрофического гастрита, ассоциированного с инфекцией Helicobacter pylori, меры профилактики // Вопросы онкологии. – 2006. – Т. 52, № 2. – С. 223-229. Pavlovich I.M., Golofeevskiy V.Yu., Kalinovskiy V.P. Predopukholevyy potentsial khronicheskogo atroficheskogo gastrita, assotsiirovannogo s infektsiey Helicobacter pylori, mery profilaktiki [Precancerous Helicobacter pylori-associated potential of atrophic gastritis Prevention]. Voprosy onkologii – Problems in oncology, 2006, vol. 52, no. 2, pp. 223-229.

3. Шварцбурд П.М. Хроническое воспаление повышает риск развития эпителиальных новообразований, индуцируя предраковое микроокружение: анализ механизмов дисрегуляции // Вопросы онкологии. – 2006. – Т. 52, № 2. – С. 137-144. Shvartsburd P.M. Hronicheskoe vospalenie povyshaet risk razvitiya epitelial`nykh novoobrazovaniy, indutsiruya predrakovoe mikrookruzhenie: analiz mekhanizmov disregulyatsii [Chronic inflammation increases risk of epithelial neoplasia by inducing precancerous microenvironment: an evaluation of pathways of disregulation]. Voprosy onkologii – Problems in oncology, 2006, vol. 52, no. 2, pp. 137-144.

4. Apte S.H., Groves P., Olver S., Baz A., Doolan D.L., Kelso A., Kienzle N. IFN-gamma inhibits IL-4- induced type 2 cytokine expression by CD8 T cells in vivo and modulates the anti-tumor response. J. Immunol., 2010, vol. 185, no. 2, pp. 998-1004.

5. Botto S., Streblow D.N., DeFilippis V., White L., Kreklywich C.N., Smith P.P., Caposio P. IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of surviving. Blood, 2011, vol. 117, no. 1, pp. 352-361.

6. Canetti C.A., Leung B.P., Culshaw S., McInnes I.B., Cunha F.Q., Liew F.Y. IL-18 enhances collageninduced arthritis by recruiting neutrophils via TNF-alpha and leukotriene B4. J. Immunol., 2003, vol. 171, no. 2, pp. 1009-1015.

7. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process – First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res., 1992, vol. 52, no. 24, pp. 6735-6740.

8. Dinarello C.A., Novick D., Rubinstein M., Lonnemann G. Interleukin 18 and interleukin 18 binding protein: possible role in immunosuppression of chronic renal failure. Blood Purif., 2003, vol. 21, no. 3, pp. 258-270.

9. Dzierzanowska-Fangrat K., Michalkiewicz J., Cielecka-Kuszyk J., Nowak M., Celinska-Cedro D., Rozynek E., Dzierzanowska D., Crabtree J.E. Enhanced gastric IL-18 mRNA expression in Helicobacter pylori-infected children is associated with macrophage infiltration, IL-8, and IL-1 beta mRNA expression. Eur. J. Gastroenterol. Hepatol., 2008, vol. 20, no. 4, pp. 314-319.

10. Evans C., Morrison I., Heriot A.G., Bartlett J.B., Finlayson C., Dalgleish A.G., Kumar D. The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival. Br. J. Cancer, 2006, vol. 94, no. 10, pp. 1412-1419.

11. Fenton J.I., Birmingham J.M. Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3. Mol. Carcinog., 2010, vol. 49, no. 7, pp. 700-709.

12. Fujita K., Ewing C.M., Isaacs W.B., Pavlovich C.P. Immunomodulatory IL-18 binding protein is produced by prostate cancer cells and its levels in urine and serum correlate with tumor status. Int. J. Cancer, 2011, vol. 129, no. 2, pp. 424-432.

13. Galley H.F., El Sakka N.E., Webster N.R., Lowes D.A., Cuthbertson B.H. Activated protein C inhibits chemotaxis and interleukin-6 release by human neutrophils without affecting other neutrophil functions. Br. J. Anaesth., 2008, vol. 100, no. 6, pp. 815-819.

14. Jablonska E., Jablonski J. Effect of IL-18 on the release of IL-6 and its soluble receptors: sIL-6Ralpha and sgp130 by human neutrophils. Immunol. Invest., 2002, vol. 31, no. 3-4, pp. 159-167.

15. Kang T.H., Mao C.P., He L., Tsai Y.C., Liu K., La V., Wu T.C., Hung C.F. Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced antitumor effects. PLoS One, 2012, vol. 7, no. 4, e35141 p.

16. Karthikeyan B., Kalishwaralal K., Sheikpranbabu S., Deepak V., Haribalaganesh R., Gurunathan S. Gold nanoparticles downregulate VEGF-and IL-1β-induced cell proliferation through Src kinase in retinal pigment epithelial cells. Exp. Eye Res., 2010, vol. 91, no. 5, pp. 769-778.

17. Kim J., Kim C., Kim T.S., Bang S.I., Yang Y., Park H., Cho D. IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway. Biochem. Biophys. Res. Commun., 2006, vol. 344, no. 4, pp. 1284-1289.

18. Kim K.E., Song H., Hahm C., Yoon S.Y., Park S., Lee H.R., Hur D.Y., Kim T., Kim C.H., Bang S.I., Bang J.W., Park H., Cho D.H. Expression of ADAM33 is a novel regulatory mechanism in IL-18-secreted process in gastric cancer. J. Immunol., 2009, vol. 182, no. 6, pp. 3548-3555.

19. Min Y.G., Rhee C.S., Kwon S.H., Lee K.S., Yun J.B. Effects of IL-1 beta, TNF-alpha, and TGF-beta on proliferation of human nasal epithelial cells in vitro. Am. J. Rhinol., 1998, vol. 12, no. 4, pp. 279-282.

20. Multhoff G., Molls M., Radons J. Chronic inflammation in cancer development. Front. Immunol., 2011, vol. 2, pp. 98.

21. Ning Y., Manegold P.C., Hong Y.K., Zhang W., Pohl A., Lurje G., Winder T., Yang D., LaBonte M.J., Wilson P.M., Ladner R.D., Lenz H.J. Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models. Int. J. Cancer., 2011, vol. 128, no. 9, pp. 2038-2049.

22. Paulukat J., Bosmann M., Nold M., Garkisch S., Kampfer H., Frank S., Raedle J., Zeuzem S., Pfeilschifter J., Muhl H. Expression and release of IL-18 binding protein in response to IFN-gamma. J. Immunol., 2001, vol. 167, no. 12, pp. 7038-7043.

23. Ruegg C. Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. J. Leukoc. Biol., 2006, vol. 80, no. 4, pp. 682-684.

24. Stein P., Weber M., Prufer S., Schmid B., Schmitt E., Probst H.C., Waisman A., Langguth P., Schild H., Radsak M.P. Regulatory T cells and IL-10 independently counterregulate cytotoxic T lymphocyte responses induced by transcutaneous immunization. PLoS One, 2011, vol. 6, no. 11, e27911 p.

25. Tanno T., Matsui W. Development and maintenance of cancer stem cells under chronic inflammation. J. Nihon. Med. Sch., 2011, vol. 78, no. 3, pp. 138-145.

26. Vannella L., Lahner E., Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal. World J. Gastroenterol., 2012, vol. 18, no. 12, pp. 1279-1285.

27. Wheelhouse N.M., Chan Y.S., Gillies S.E., Caldwell H., Ross J.A., Harrison D.J., Prost S. TNF-alpha induced DNA damage in primary murine hepatocytes. Int. J. Mol. Med., 2003, vol. 12, no. 6, pp. 889-894.

28. Yoo J.K., Kwon H., Khil L.Y., Zhang L., Jun H.S., Yoon J.W. IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways. J. Immunol., 2005, vol. 175, no. 12, pp. 8280-8286.

29. Zhang L., Hou Y., Wu K., Li D. Comparative proteomics analysis of chronic atrophic gastritis: changes of protein expression in chronic atrophic gastritis without Helicobacter pylori infection. Braz. J. Med. Biol. Res., 2012, vol. 45, no. 3, pp. 273-283.