Expresión local de citocinas, grado de lesión de la mucosa gástrica e influencia de las helmintiasis intestinales en adultos venezolanos infectados por "Helicobacter pylori"

Abstract

Helicobacter pylori infection is associated to a variety of benign and malignant gastroduodenal features, in which the host immune response plays a crucial pathogenic role. During the last years, experimental and epidemiological evidences have been presented in favor of a possible role of intestinal helminths as modifiers of the Th1-predominant immune response triggered by H. pylori infection. However, this immunomodulatory effect has not been studied in humans, in regard to cytokines-dependant local immune response. The aim of the present research was to determine if helminths intestinal coinfection is associated to changes in proinflammatory and/or antiinflammatory cytokines local expression and the gastric mucosa injury degree, in individuals with gastritis associated to H. pylori infection. After applying strict inclusion and exclusion criteria, forty-six symptomatic adults from the Zulia State, northwest Venezuela, were selected, provided endoscopic evidences of gastropathy. They were classified into three groups, according to the status of H. pylori and helminths infections: Hp-/helm- (17), Hp+/helm- (18) and Hp+/helm+ (11). Each patient underwent an upper gastrointestinal endoscopy, histopathological analysis of gastric mucosal biopsies, and descriptive-semiquantitative and quantitative immunohistochemistry with peroxidasa staining, for detecting cytokines IL-1β, TNF-α, IFN-γ and IL-4, in paraffin sections of the antral gastric mucosa. The statistics Chi Square or Fisher Exact Test, Kruskal-Wallis Test, Mann-Whitney U and Spearman Correlation Coefficient were applied to determine the significance of findings (p<0,05). The expression of the 4 cytokines was identified in all the groups, predominantly in the epithelium and upper third of the mucosal lamina propria. In the control group (HP-) were evident: a low expression of all the cytokines, mild mucosal injuries and a scarce lymphoplasmacytic infiltration. In the group Hp+/helm-, a significant increase in the proinflammatory cytokines expression was evident, mainly IL-1, without changes in the IL-4 expression degree, indicating a Th1-predominant immune response associated to H. pylori infection. Accordingly, a high percentage of such individuals presented active atrophic chronic gastritis and a risk index of gastric cancer relatively low, but significantly higher than the control group. In the helminths-coinfected group, IL-4 expression increased significantly, in conjunction with a negative regulation of the 3 proinflammatory cytokines, thus exhibiting the characteristic pattern of a Th2-predominant immune response. In the histopathological evaluation, mild changes were detected, more evident in the gastric corpus, tending to a minor grade of mononuclear cells infiltration, lower frequency of mucosal atrophy and decreased risk index of gastric cancer. In conclusion, intestinal helminths coinfection modulates the local cytokines response characteristically Th1-predominant in the gastric mucosa of humans H. pylori infected, favoring the balance towards a Th2-predominant response. Possible favorable consequences of this immunomodulatory effect might be more evident in populations with a high risk of gastric carcinogenesis