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., phagocytosis, killing, and antibacterial activity), serum autoantibodies (antineutrophil cytoplasmic antibodies [ANCA] and anti-lactoferrin [LF] antibodies), and plasma endotoxins in patients affected by ulcerative colitis (UC) and Crohn'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 Truelove's criteria in patients with UC and the Crohn's Disease Activity Index (CDAI) in patients with CD. Candida albicans served as a target for evaluation of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes (MO), whereas Salmonella typhi was used for assessing lymphocyte-mediated antibacterial activity. ANCA were detected by indirect immunofluorescence, whereas anti-LF antibodies were assayed by means of enzyme-linked immunosorbent assay. Plasma endotoxins were measured by Limulus amoebocyte lysate assay.


RESULTS
Phagocytosis and killing exerted by PMN and MO, as well as lymphocyte-mediated antibacterial activity, were significantly reduced (p < 0.0001) in patients affected by UC and CD in comparison with controls, irrespective 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 with CD, whereas anti-LF antibodies were detected in 31 (44%) UC patients and in six (19%) CD patients. No significant differences in phagocytosis and killing 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 presence did not affect PMN-mediated phagocytosis and killing. Finally, plasma endotoxins may contribute to the chronic inflammatory status, likely by inducing release of proinflammatory mediators.
Caradonna
L
L
IRCCS for Gastroenterological Diseases, Castellana Grotte, Bari, Italy.
Amati
L
L
Lella
P
P
Jirillo
E
E
Caccavo
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001770:Blood Bactericidal Activity; D016923:Cell Death; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D003424:Crohn Disease / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D007781:Lactoferrin / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D004731:Endotoxins; D007781:Lactoferrin