CYTOKINES AS PREDICTORS OF INTESTINAL METAPLASIA OF STOMACH

An inflammatory process accompanied by the changes in mucosal microbiota is underlying the gastroduodenal diseases. Chronic inflammation of gastric mucosa is developed and supported by secretion of pro-inflammatory and anti-inflammatory cytokines by epithelial cells and immune cells induced by Helicobacter pylori and other microorganisms. Under the conditions of dysbiosis and immune dysregulation, gastric epithelial layer becomes like intestinal or colonic epithelium. The aim of this work was to determine diagnostic and prognostic value of cytokines in intestinal metaplasia of gastric epithelium. 
204 patients with exacerbation of chronic gastritis, gastric ulcer, gastric polyposis and 40 healthy volunteers were included into the study, under their informed consent. The gastric biopsies were sampled by means of esophagogastroduodenoscopy (for histological and microbiological examination), along with drawing 5 ml of venous blood with serum separation (for enzyme immunoassay). Serum cytokine levels were studied by solidphase enzyme immunoassay. In statistical evaluation of the results, we have calculated sensitivity, specificity of indexes, logistic regression equations, characteristic curves were built with the definition of the index of consistency of the model by the area under the curves (AUC).
Histological examination of gastric biopsies showed features of intestinal metaplasia in 61 patients (29.90%), colonic metaplasia was found in 40 cases (19.61%), being absent in healthy volunteers. The greatest sensitivity of intestinal metaplasia was observed for plasma levels of interleukin (IL)-6, IL-4, erythropoietin (EPO), tumor necrosis factor (TNF)α, IL-18, vascular endothelial growth factor (VEGF), interferon (IFN)α levels; in colonic metaplasia, for receptor antagonist IL-1β (IL-1ra), IL-8, EPO, IL-18, monocyte chemoattractant protein (MCP)-1, VEGF, IFNα, IL-1β, IL-6, IL-17. An increase in IL-6, EPO, IL-18, VEGF, IFNα were also common, thus indicative for changed functional activity of cytokines due to microbial contamination of gastric mucosa, tissue hypoxia with activation of angiogenesis, confirming a transition of intestinal metaplasia to gastric carcinogenesis. The greatest specificity in intestinal metaplasia was observed for IL-1β, IL-1ra, IL-8, IL-17, IL-2, IL-10; in colonic metaplasia, for IL-18, IFNα, IL-4, МСР-1, VEGF. In the intestinal metaplasia, the AUC interval was higher than 0.7 for IL-2, higher than 0.65, in VEG; in colonic metaplasia > 0.91, for IL- 18, VEGF, МСР-1, IFNα, having a significance level of < 0.001. The obtained prognostic models of intestinal metaplasia of gastric epithelium, according to the AUC index, had very good (Table 2, formula 1) and excellent quality (Table 2, 3, formula 2-11), confirmed by a high percent of cases which were correctly classified of metaplasia.
   Determination of serum cytokines in intestinal metaplasia of gastric epithelium is of diagnostic and prognostic value, and should be used for early diagnosis of precancerous conditions of the gastric mucosa, both as single indexes (IL-2, VEGF), and combined indicators, according to the calculated logistic regression equations.

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