TRANSFORMING GROWTH FACTOR-Β1,2,3 AND INTERLEUKIN-6 IN BLOOD IN PATIENTS WITH ULCERATIVE COLITIS OF VARIOUS DISEASE ACTIVITY ACCORDING TO CLINICAL PICTURE AND ENDOSCOPIC DATA

DOI: https://doi.org/None

E.A. Konovich, I.L. Khalif, , K.E. Shirokikh, M.V. Shapina A.N. Rizhikh State Scientific Centre for Coloproctology, Salyama Adilya str., 2, Moscow, 123423, Russian Federation

Introduction. Ulcerative colitis is a chronic inflammatory disease. Misbalance in innate and adaptive immunity including cytokines plays a significant role in its pathogenesis. Objective. To determine levels of cytokine TGFβ1, 2, 3, and IL6 in blood of patients with ulcerative colitis of various disease activity according to clinical picture and endoscopic data. Methods. Serum samples of 27 patients with pancolitis were taken. Moderate clinical and endoscopic activity and severe clinical and endoscopic activity of ulcerative colitis were observed in 13 and 14 patients, respectively. Cytokines were analyzed on the protein analyzer Bio-Plex (Bio-Rad, USA). Results. Decrease of TGFβ1 concentration was found in 53,8%, TGFβ2 and TGFβ3 in 38,4% of patients with moderate ulcerative colitis. Increase of TGFβ2 concentration was found in 30,7% and TGFβ3 – in 61,5% of patients with severe ulcerative colitis. Levels of IL6 were significantly elevated in patients with severe inflammatory activity. Reduction of TGFβ in combination with a lack of circulating IL6 was observed in 58,3% of patients with moderate activity and 7,7% of patients with severe inflammatory activity (p0,05), respectively. Conclusion. Moderate clinical and endoscopic activity of ulcerative colitis is associated with a lack of TGFβ1, 2, 3. Progression of inflammation to severe activity is associated with an increase of IL6 and TGFβ2, 3 levels. It is also possible that TGFβ gains pro-inflammatory function.
Keywords: 
ulcerative colitis, cytokines TGFβ1, 2, 3 and IL6

Список литературы: 
  1. Mihaylova T.L., Halif I.L. Yazvennyy kolit. Klinicheskaya harakteristika. V kn.: Nespecificheskie vospalitel`nye zabolevaniya kishechnika. Red. Vorob`ev G.I. i Halif I.L. Miklosh. 2008; 247–87.[Mikhailova T.L., Khalif I.L., Ulcerative colitis. Clinical characteristics. In book: Nonspecific inflammatory bowel diseases. Ed. Vorobyov G.I., Khalif I.L. Miklosh. 2008; 247–87 (in Russian)]
  2. Konovich E.A., Halif I.L., Shapina M.V. Immunopatogenez vospalitel`nyh zabolevaniy kishechnika. Rossiyskiy zhurnal gastroe`nterologii, gepatologii, koloproktologii. 2013; 4: 69–77.[Konovich E.A., Khalif I.L., Shapina M.V. Immunopathogenesis of inflammatory bowel diseases. Russian journal of gastroenterology, hepatology, coloproctology. 2013; 4: 69–77 (in Russian)]
  3. Műzes G., Molnar B., Tulassay Z., Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World J. Gastroenterol. 2012; 18: 5848–61.
  4. Gorelik L., Flavell R.A. Transforming growth factor-β in T-cell biology. Nature Rev. Immunol. 2002; 2: 46–53.
  5. Feagins L.A. Role of Transforming Growth Factor-β in Inflammatory Bowel Disease and Colitis-associated Colon Cancer. Inflammatory Bowel Diseases, 2010; 16: 1963–8.
  6. Li MO., Wan Y.Y., Sanjabi S., Robertson A.K., Flawell R.A. Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunology. 2006; 24: 99–146.
  7. Schmidt-Weber C.B., Blaser K. Regulation and role of transforming growth factor-beta in immune tolerance induction and inflammation. Curr. Opin. Immunology. 2004; 16: 709–16.
  8. Kulkarni A.B., Ward J.M., Yaswen L, Transforming growth factor-beta I null mice. An animal model for inflammatory disorders. Am. J. Pathology. 1995; 146: 264–75.
  9. Di Sabatino A., Pickard K.M., Rampton D. Blockade of transforming growth factor beta upregulates T-box transcription factor T-beta, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa. Gut. 2008; 57: 605–12.
  10. Veselov V.V. E`ndoskopicheskaya diagnostika nespecificheskih vospalitel`nyh zabolevaniy kishechnika. V kn.: Nespecificheskie vospalitel`nye zabolevaniya kishechnika. Red. Vorob`ev G.I. i Halif I.L. Miklosh. 2008; 191–4. [Veselov V.V. Endoscopic diagnosis of nonspecific inflammatory bowel diseases. In book: Nonspecific inflammatory bowel diseases. Ed. Vorobyov G.I., Khalif I.L., Miklosh. 2008; 191–4 (in Russian)]
  11. Wiercinska-Drapalo A., Flisiak R., Prokopowicz D. Effect of ulcerative colitis treatment on transforming growth factor β1 in plasma and rectal mucosa. Regulatory Peptides. 2003; 113: 57–61.
  12. Stadnicki A., Machnik G., Klimacka-Nawrot E., Wolanska-Karut A., Labusek K. Transforming growth factor-β1 and its receptors in patients with ulcerative colitis. Internat. Immunopharmacology. 2009; 9: 761–6.
  13. Wedrychowicz A., Kowalska-Duplaga K., Jedynak-Wasowicz U., Pieczarkowsli S., Sladek M., Tomasik P., Fyderek K. Serum Concentrations of VEGF and TGF-β1 during Exclusive Enteral Nutrition in IBD. J. Pediatr. Gastroenterology Nutrition. 2011; 53: 150–5.
  14. Kilic Z.M., Avaz S., Ozin Y., Nadir I., Cakal B., Ulker A. Plasma transforming growth factor-beta1 level in inflammatory bowel disease. Turk. J. Gastroenterology. 2009; 20: 165–70.
  15. Liberek A., Kmiec Z., Kartanowicz D., Wierzbicki P., Stanislawowski M., Kaszubowska L., Luczak G., Gora-Gebka M., Landowski P. The mRNA level of the transforming growth factor β1 gene, but not the amount of the gene product, can be considered as a potential prognostic parameter in inflammatory bowel diseases in children. Internat. J. Colorectal Disease. 2013; 28: 165–72.
  16. Manolova I., Gerenova J., Ivanova M. Serum levels of transforming growth factor-β1 (TGF-β1) in patients with systemic lupus erythematosus and Hashimoto’s thyroiditis. Eur. Cytokine Netw. 2013; 24 (1): 69–74.
  17. Niu Q., Cai B., Huang Z.C., Shi Y.Y., Wang L.L. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol. Int. 2012; 32 (9): 2731–6.
  18. Olivieri A., De Angelis S., Dionisi S., D’Annunzio G., Locatelli M., Marinaro M., Bonato V., Amendola A., Songini M., Velluzzi F., Schirru C., Cotichini R., Stazi M.A., Dotta F., Lorini R., Bottazzo G.F., Boirivant M. Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans. Clin. Exp. Immunol. 2010; 162 (3): 407–14.
  19. Chen J.G., Lai W., Jiang Y. Expression of Th17/Treg cell in patients with psoriasis arthritis and its clinical significance. Zhongguo Yi XueKeXue Yuan XueBao. 2012; 34 (6): 617–20.
  20. Cai Z., Zhang W., Li M., Yue Y., Yang F., Yu L., Cao X., Wang J. TGF-beta1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4(+) Foxp3(+) regulatory T cells. Cell Mol. Immunol. 2010; 7 (1): 35–43.
  21. Mudter J., Neurath M.F. IL-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance. Inflammatory Bowel disease. 2007; 13: 1016–23.
  22. Konovich E.A., Halif I.L., Shapina M.V., Shirokih K.E. Citokiny syvorotki krovi u bol`nyh yazvennym kolitom s razlichnoy klinicheskoy aktivnost`yu. Rossiyskiy zhurnal.gastroe`nterologii, gepatologii, koloproktologii. 2014; 4: 51–6.[Konovich E.A., Khalif I.L., Shapina M.V., Shirokikh K.E. Serum cytokines in patients with ulcerative colitis with different clinical activity. Russian journal of gastroenterology, hepatology, coloproctology. 2014; 4: 51–6 (in Russian)]
  23. Bettelli E., Carrier Y., Gao W. Reciprocal developmental pathways for the generation of pathogenic effector Th17 and regulatory T-cells. Nature. 2006; 441: 235–8.
  24. Saxena V., Lienesch D.W., Zhou M., Bommireddy R., Azhar M., Doetschman T., Singh R. Dual Roles of Immunoregulatory Cytokine TGF-β in the Pathogenesis of Autoimmunity-Mediated Organ Damage. J. Immunology. 2008; 180: 1903–12.