Evidence of chronic inflammation in morphologically normal small intestineof cystic fibrosis patients

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conduct ance regulator gene and characteristically leads to prominent lung and panc reatic malfunctions. Although an inflammatory reaction is normally observed in the CF airways, no studies have been performed to establish whether a c hronic inflammatory response is also present in the CF intestine. We have i nvestigated whether immunologic alterations and signs of inflammation are o bserved in CF small intestine. Fourteen CF, 20 negative, and four disease c ontrols underwent duodenal endoscopy for diagnostic purposes. Two CF patien ts were rebiopsied, one after 3 mo of an elemental diet and the other after 2 wk of pancreatic enzyme withdrawal. In three CF and 10 controls, in vitr o small intestine organ cultures were also performed. Expression of ICAM-1, IL-2 receptor, IL-2, IFN-gamma, CD80, and transferrin receptor was studied by immunohistochemistry before and after in vitro organ culture. In CF sma ll intestine, an increased number of lamina propria mononuclear cells expre ss ICAM-1 [mean 114 (SD 82.8), p < 0.001 versus controls], CD25 [20.2 (18.7 ), p < 0.01], IL-2 [23.6 (13.7), p < 0.05], and IFN-gamma [19 (15.9), p < 0 .05], whereas villus enterocytes highly express transferrin receptor. Reduc ed expression of immunologic markers wets observed after 24 h of in vitro c ulture in all three CF patients as well as in the patient kept on elemental diet for 3 mo. These results indicate that chronic inflammation is observe d in CF duodenum and suggest that the perturbation of local mucosal immune response may contribute to the overall clinical picture in CF patients.