IL-10 secretion and sensitivity in normal human intestine and inflammatory bowel disease.
Interleukin-10 (IL-10) deficiency in gene knockout mice causes chronic enterocolitis. We hypothesized that inflammation in human inflammatory bowel disease might result from innate alterations in the IL-10 pathway. Serum, supernatants, and mRNA of peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) derived from inflamed (LPMC-i) and noninflamed colonic mucosa (LPMC-ni) were collected from patients with Crohn's colitis, ulcerative colitis, and controls. IL-10 protein concentrations and IL-10 mRNA were examined in response to PMA/CD3 or PHA stimulation. The response to rhIL-10 was assessed by inhibition of tumor necrosis factor-alpha (TNF-alpha), IL-6, and interferon-gamma (IFN-gamma) production. Serum IL-10 levels of inflammatory bowel disease (IBD) patients were within the normal range. IL-10 concentrations in supernatants from LPMC-i were significantly lower than from LPMC-ni or PBMC. No difference was seen between samples from ulcerative colitis and Crohn's disease. IL-10 mRNA was detected in 0/4 LPMC-i samples compared to 1/6 LPMC-ni and 6/6 PBMC. RhIL-10 inhibited TNF-alpha, IL-6, and IFN-gamma synthesis in PBMC. This effect was strongly diminished in LPMC. Disease-specific alterations were not detected. Our data suggest that LPMC derived from inflamed colonic mucosa have a reduced ability to produce and to respond to rhIL-10. A disease-specific alteration in the IL-10 pathway, however, was not found.
Gasche
C
C
Department of Gastroenterology and Hepatology, University of Vienna, Austria. cgasche@ucsd.edu
Bakos
S
S
Dejaco
C
C
Tillinger
W
W
Zakeri
S
S
Reinisch
W
W
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D003113:Colonoscopy; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10