Immune Suppression by Cyclosporin A Inhibits Phytohemagglutinin-induced Precocious Gut Maturation in Suckling Rats

Enteral exposure to the lectin phytohemagglutinin (PHA) provokes precocious gut maturation in suckling rats coinciding with an early expansion of intestinal mucosal T and B lymphocytes. Here, the role of the immune system in neonatal gut growth and maturation was further studied. The effects of immunosuppression by cyclosporine A (CyA), 7.5 µg/g of body weight, injected 12 hours before and then daily after the intragastric gavage of PHA, 100 µg/g body weight, to 14-day-old suckling rats were studied after 4 and 12 hours and later after 72 hours. At 4 hours after PHA feeding, an early rapid increase in the intestinal levels of the proinflammatory cytokines interleukin-6, interleukin-1ß, and tumor necrosis factor was obtained, and the CyA treatment did not prevent the temporary PHA-induced intestinal disturbance seen at 12 hours. Later, at 72 hours after PHA gavage the CyA treatment significantly counteracted the PHA-induced gut changes with a decrease in small intestinal growth, a delay in the appearance of adult-phenotype enterocytes in the distal small intestinal, and total inhibition of the PHA-induced pancreas development. Additionally, the increase in plasma level of the acute phase protein, haptoglobin, after PHA feeding was dampened by CyA. The results indicate that proinflammatory cytokines are involved in the early recruitment of lymphocytes to the gut after PHA challenge, and that the ensuing precocious gut maturation is dependent on activation of the immune system, presumably T cells, in suckling rats.