Inflammatory bowel disease is associated with increased mucosal levels of bactericidal permeability-increasing protein

Background & Aims: Clinical sepsis seldom accompanies inflammatory bowel disease. The aim of this study was to measure colonic mucosal levels of the neutrophil product bactericidal/permeability-increasing protein (BPI), which kills gram-negative bacteria in addition to inactivating endotoxin. Methods: Enzyme-linked immunosorbent assay and immunohistochemistry for BPI were performed on homogenates and tissue sections of biopsy specimens from patients with ulcerative colitis (n = 11) and Crohn's disease (n = 5) and from normal controls (n = 5). Results: Mucosal neutrophil content (144 +/- 23 vs. 35 +/- 9 neutrophils/mg protein; P < 0.007) and BPI content (2.07 +/- 0.75 vs. 0.12 +/- 0.02 ng/mg protein; P < 0.002) were greater in the colitis groups and correlated closely (r = 0.68; P < 0.001). This relationship held for both ulcerative colitis (P < 0.002) and Crohn's disease (P < 0.01) with a trend towards greater levels in Crohn's disease. There was a trend towards higher BPI levels with an increasing endoscopic inflammation score (grade I, 1.32 +/- 0.6 ng/mg protein; grade II, 2.82 +/- 1.4 ng/mg protein), Immunohistochemistry and the biopsy culture showed BPI to be both intracellular and extracellular, to be present in the crypt lumen, and to be released into incubating medium. Conclusions: Mucosal levels of BPI ave increased in colitis. Such localization may ameliorate mucosal responses to gram-negative bacteria and their products.