Colonic cytokines for severe ulcerative colitis

Aim of investigation. To assess colonic cytokines profile at severe ulcerative colitis (UC). Material and methods. Overall 48 biopsy specimens of colonic mucosa obtained at resection operations in 7 patients with total form of UC were investigated. All patients underwent total colectomy for severe treatment-resistant UC. Activity of inflammatory process was determined by severity of erosive and ulcerative lesions of the colon. Cytokine concentration was evaluated in supernatant fluid after centrifugal separation of 10 mg biopsy specimen homogenate by the protein analyzer «Bio-Plex» («Bio-Rad», USA). Colonic mucosa biopsy specimens of unaffected parts of the large intestine resected in 10 patients with colorectal cancer were used as controls. Results. Tissue levels of IL-1β, IL-8, IL-6, TNF-α (tumor necrosis factor-α), IFN-γ (interferon-γ), IL-17 and IL-12 in biopsy specimens the large intestine of UC patients were significantly elevated. The most significant elevation was found for IL-8 and IL-1β, with the ratio of 3:1 (in the control group 0,35:1). The cytokine content in biopsy specimens of the large intestine has been increased in comparison to terminal portion of the small intestine, and the cytokine level in the left and transverse part of the colon was higher, than in cecum and ascending colon. At severe inflammation as compared to moderate inflammation the most significant increase was found for IL-8, IL-6 and TNF-α. Cytokine profile with the prevalence of IL-1β (IL-1β>IL-8>IL-6 (IFN-γ)>TNF-α) was observed in 14 (77,7%) of 18 biopsy specimens with moderate inflammation while similar cytokine pattern was observed in 9 (47,3%) of 19 biopsy specimens with severe inflammation (p=0,05). Domination of IL-8 (IL-8> IL-1β> IL-6 (TNF-α)> TNF-α (IL-6)) in cytokine profile was found in 3 of 18 (16,6%) biopsy specimens with moderate and in 9 of 19 (47,3%) biopsy specimens with a severe inflammation (p<0,05). Cytokines IL-2, IL-4, IL-5, IL-7, IL-10 and IL-13 when undetected neither in UC patients, nor in control group. Conclusions. Significant increase in proinflammatory cytokine level with prevalence of IL-1β and IL-8 at moderate and severe erosive - ulcerative involvement respectively was observed in colonic mucosa biopsies in comparison to terminal ileum of UC patients and control group; in the left part and transverse colon versus ascending colon and caecum of UC patients. Elevation of IFN-γ and IL-17 content at severe inflammation indicates presence of common mechanisms in ulcerative colitis disease and Crohn's disease pathogenesis.

язвенный колит, толстая кишка, цитокины

1. Веселов В.В. Эндоскопическая диагностика неспецифических воспалительных заболеваний кишечника. В кн.: Неспецифические воспалительные заболевания кишечника / Под ред. Г.И. Воробьева, И.Л. Халифа. М.: Миклош, 2008:190-4.

2. Конович Е.А., Халиф И.Л., Шапина М.В. Иммунопатогенез воспалительных заболеваний кишечника. Рос журн гастроэнтерол гепатол колопроктол 2013; 23(4):69-77.

3. Лазебник Л.Б., Царегородцева Т.М., Серова Т.И. и др. Цитокины и цитокинотерапия при болезнях органов пищеварения. Тер арх 2004; 4:69-72.

4. Михайлова Т.Л., Халиф И.Л. Язвенный колит. Клиническая характеристика. В кн.: Неспецифические воспалительные заболевания кишечника / Под ред. Г.И. Воробьева, И.Л. Халифа. М.: Миклош, 2008:13647.

5. Фиокки Клаудио. Этиопатогенез воспалительных заболеваний кишечника. Колопроктология 2015; 1:5-20 (пер. с англ.).

6. Халиф И.Л., Михайлова Т.Л., Белоусова Е.А. Консервативное лечение язвенного колита и болезни Крона. В кн.: Неспецифические воспалительные заболевания кишечника / Под ред. Г.И. Воробьева, И.Л. Халифа. М.: Миклош, 2008:247-87.

7. Ягода А.В., Павленко В.В. Иммуновоспалительные аспекты язвенного колита. Иммунология 2002; 3:178-81.

8. Begue B., Wajant H., Bambou J.C., et al. Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions. Gastroenterology 2006; 130:1962-74.

9. Biancheri P., Di Sabatino A., Ammoscato F., et al. Absence of a role for interleukin-13 in inflammatory bowel disease. Eur J Immunol 2014; 44:370-85.

10. MacDonald T.T., Monteleone G. Adaptive immunity: Effector and inhibitory cytokine pathways in gut inflammation. In: Targan S.R., Shanahan F., Karp L.C., eds. Inflammatory bowel disease. Translating basic science into clinical practice. Chichester: Wiley-Blackwell; 2010:8291.

11. Maillard M.H., Snapper S.B. Cytokines and chemokines in mucosal homeostasis. In: Targan S.R., Shanahan F., Karp L.C., eds. Inflammatory bowel disease. Translating basic science into clinical practice. Chichester: WileyBlackwell; 2010:119-56.

12. Mitsuyama K., Toyonaga A., Sasaki E., et al. IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn΄s disease. Clin Exp Immunol 1994; 96:432-6.

13. Mudter J., Neurath M.F. IL-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance. Inflamm Bowel Dis 2007; 13:1016-23.

14. Műzes G., Molnar B., Tulassay Z., Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World J Gastroenterol 2012; 18(41):5848-61.

15. Pushparaj P., Dong Li, Komai-Koma M., et al. Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology 2013; 140:70-7.

16. Reinecker H.-C. Steffen M., Witthoeft T., et al. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1β by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn΄s disease. Clin Exp Immunol 1993; 94:174-81.