Phagocytosis, killing, lymphocyte-mediated antibacterial activity, serum autoantibodies, and plasma endotoxins in inflammatory bowel disease

OBJECTIVE: Alteration of mucosal and systemic immune responses may play an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to evaluate natural immune responses (i.e., phagocyt osis, killing, and antibacterial activity), serum autoantibodies (antineutr ophil cytoplasmic antibodies [ANCA] and anti-lactoferrin [LF] antibodies), and plasma endotoxins in patients affected by ulcerative colitis (UC) and C rohn's disease (CD). METHODS: Blood samples were obtained from 71 patients with UC, 32 patients with CD, and 32 control subjects. Disease activity was scored using Truelov e's criteria in patients with UC and the Crohn's Disease Activity Index (CD AI) in patients with CD. Candida albicans served as a target for evaluation of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and m onocytes (MO), whereas Salmonella typhi was used for assessing lymphocyte-m ediated antibacterial activity. ANCA were detected by indirect immunofluore scence, whereas anti-LF antibodies were assayed by means of enzyme-linked i mmunosorbent assay. Plasma endotoxins were measured by Limulus amoebocyte l ysate assay. RESULTS: Phagocytosis and killing exerted by PMN and MO, as well as lymphoc yte-mediated antibacterial activity, were significantly reduced (p < 0.0001 ) in patients affected by UC and CD in comparison with controls, irrespecti ve of either disease activity or treatment. Plasma endotoxins were detected in 12/71 (17%) patients with UC, and in 10/32 (31%) patients with CD. ANCA were present in 42/71 (59%) patients with UC and in 3/32 (9%) patients wit h CD, whereas anti-LF antibodies were detected in 31 (44%) UC patients and in six (19%) CD patients. No significant differences in phagocytosis and ki lling exerted by PMN were found between ANCA-positive and ANCA-negative UC patients. CONCLUSIONS: Our data demonstrate an impairment of natural immunity exerted by peripheral blood phagocytes and lymphocytes in patients with UC and CD. ANCA and anti-LF antibodies were present mainly in UC patients but their p resence did not affect PMN-mediated phagocytosis and killing. Finally, plas ma endotoxins may contribute to the chronic inflammatory status, likely by inducing release of proinflammatory mediators. (Am J Gastroenterol 2000; 95 .1495-1502. (C) 2000 by Am. Cell. of Gastroenterology).