Emerging evidence revealed that intestinal infection and inflammation play a crucial role in the occurrence and development of IBS [8, 9]. Previous study above 70% D-IBS and 10% C-IBS were involved in infection . In the present study, we showed that 20 of 38 (above 52%) D-IBS and C-IBS patients had an intestinal infection and bacillary dysentery, which confirmed the role of infection in the disease. Moreover, we found that the expression of cytokines was imbalanced and shifted between T helper 1 and T helper 2 (Th1/Th2) in intestinal mucosa of PI-IBS patients, suggesting that an immune dysregulation mechanism was involved in the disease.
CD4+T cells can be categorized into Th1 and Th2 subgroups according to the differences in cytokine secretion, and the two subgroups restrain and transform mutually to maintain normal immunological function . Several studies suggested that Th1-derived cytokines IFN-γ and IL-2 in peripheral blood were significantly higher in D-IBS patients than that in healthy persons, while the Th2-derived cytokine IL-4 was significantly lower in D-IBS patients than in healthy persons , illustrating that the changes in immune balance were primarily related to decreasing cytokine secretion . In this study, our results showed that compared to non-PI-IBS patients or healthy people, Th1-derived cytokine IFN-γ expression was significantly upregulated in the intestinal mucosa of PI-IBS patients. In addition, the expression level of the Th2-derived cytokine IL-10 was significantly lower in the intestinal mucosa of PI-IBS patients. However, the expression of IFN-γ or IL-10 between the non-PI-IBS and control groups was not significantly different. These results suggested that expression of Th1-derived cytokines increased while Th2-derived cytokines decreased in PI-IBS patients, which implied that the Th1/Th2 balance was possibly shifted to Th1 immunodominance. Therefore, it is indicated that the Th1/Th2 shift would be affected by the infection. In the infectious state, the inflammatory factors would change the intestinal mucosal permeability and the subsequent immunocyte response, such as eliciting the Th1 response by microbiotic antigens. In addition, this Th1/Th2 shift may lead to sustained immunological activation and subsequent abnormal sensation through the neuro-endocrine-immunity network . However, further studies are still required to clarify the exact mechanism.
IFN-γ and IL-12 are proinflammatory factors. IFN-γ can combine with specific receptors to exert distinct effects, such as macrophage activation, promotion of Th0 cells to differentiate into Th1 cells, inhibition of cell proliferation, promotion of B cell differentiation, and antibody production. In contrast, IL-4 and IL-10 are produced by Th2 cells and are important immune regulators and anti-inflammatory factors; they inhibit Th1 cell proliferation, promote B cell proliferation, antagonize the response to antigenic stimulation, block harmful immunological responses, depress the function of mononuclear macrophages and granulocytes, and downregulate mononuclear macrophage-secreting proinflammatory factors such as IL-1β and TNF-α. IL-4 and IL-10 may decrease the mucosal inflammation that arises from Th1 cytokines. Previous studies have shown an increase in inflammatory cells, proinflammatory factors, and immunological activation in the intestinal mucosa of PI-IBS patients [13, 14]. In this study, IFN-γ expression increased and IL-10 expression decreased in the intestinal mucosa of PI-IBS patients, which implies that persistent inflammation may exist due to dysregulation of the these cytokines. Since the permeability changes in the intestinal mucosa are caused by inflammatory infections, the immunological cells’ contact with certain foods and microorganisms would easily cause activation, and lead to Th1 immunodominance. The increase of cellular immunity and the action of the secreted cytokines may result in abnormal intestinal function, motion, and a series of symptoms [15, 16]. These results are also consistent with PI-IBS symptoms [17, 18].
Some studies indicate that Th1- and Th2-derived cytokines show different expression levels in different segments of the intestine in several IBS patients and the quantity of immunocytes varies with the intestinal segments [19, 20]. We chose the ascending colon, the descending colon, and the rectum to observe whether there is variability in the expression Th1- and Th2-derived cytokines in the different locations. We did not see any significant difference in the Th1- and Th2-derived cytokines expression level in the three intestinal segments. However, a larger sample size is needed to clarify these results.