Glucagon-like peptide-2 improves intestinal immune function and diminishes bacterial translocation in a mouse model of parenteral nutrition

Parenteral nutrition (PN) is associated with increased infectious risks due to impaired intestinal immunity. Although glucagon-like peptide-2 (GLP-2) enhances the gut barrier function, it is uncertain whether it improves mucosal immunologic barrier function. We hypothesized that injecting the PN mouse model with GLP-2 improved innate and acquired immunity, and prevented bacterial translocation. Forty-eight hours after venous cannulation, male Institute of Cancer Research mice were randomly divided into 3 groups based on their diet: chow with saline (n = 10), PN (n = 9), or PN + GLP-2 (30 μg/bid/mouse, n = 10) provided for 5 days. Compared to chow, PN reduced interleukin 4 (IL-4) and IL-13 levels (P < .05, respectively), whereas, compared to PN alone, GLP-2 injection increased IL-4 and IL-13 levels (P < .05, respectively). Compared to chow, PN considerably suppressed, while GLP-2 improved, secretory phospholipase A2 (sPLA2) and cryptdin-4 expression. PN, compared to chow, considerably decreased lysozyme and polymeric immunoglobulin receptor (pIgR) levels, whereas, compared to PN, GLP-2 significantly increased these protein levels (P < .01, respectively). In tissue and luminal samples, compared to chow, PN reduced secretory immunoglobulin-A (sIgA) levels (P < .05), whereas, compared to PN alone, GLP-2 increased sIgA levels (P < .05). Functionally, more bacterial translocation was observed in the PN group compared to the chow group (P < .001), and GLP-2 injection decreased bacterial translocation to chow levels (P < .05). In summary, GLP-2 treatment may improve intestinal innate and acquired immunity, and prevent bacterial translocation in mice on total parenteral nutrition.