Cholecystokinin prevents intestinal barrier dysfunction induced by systemic inflammation in rats

Systemic inflammation consists in a primary injury to the intestinal epithelium structure. The inflammatory mediators synthesized in the acute phase contribute to the increase in intestinal permeability and bacterial translocation. Cholecystokinin (CCK) was firstly described as a gastrointestinal hormone, but immune cells express their receptors, suggesting a possible involvement of this peptide in pathophysiological processes. Our aims were to evaluate the role of CCK on intestinal permeability, bacterial translocation and production of cytokines during systemic inflammation induced by lipopolysaccharide administration (LPS). Male Wistar rats were pre-treated with proglumide (P) (non-selective CCK receptor antagonist; 30 or 50 mg/kg) or CCK (0.4 or 40 µg/kg) before LPS administration (1.5 mg/kg, i.v.). At 4 and 24h after endotoxemia induction, the intestinal permeability was evaluated by injecting FITC-dextran 4 kDa in the colon or ileum, mesenteric lymph nodes were collected for microbiological analysis and also cytokines were quantified in the plasma. Our results demonstrated that CCK administration reduces the permeability only in the colon, while P showed the opposite effect. The plasma concentrations of TNF-α, IL-1β, IL-6 and IFN-γ were significantly reduced in CCK-treated rats, while the P group showed increased synthesis of these cytokines. Furthermore, CCK prevented the bacterial translocation to the mesenteric lymph nodes at the both time-point investigated in comparison to LPS group. This data suggests a protective role for CCK preventing the intestinal barrier dysfunction induced by systemic inflammation, possibly modulating the inflammatory response.