Influence of interleukin-10 on the interleukin-1 receptor antagonist/interleukin-1 beta ratio in the colonic mucosa of ulcerative colitis.
A decrease in the ratio of IL-1ra/IL-1 beta produced regionally by the colonic mucosa of patients with ulcerative colitis (UC) is believed to play a role in the pathogenesis of UC. To investigate factors influencing intramucosal IL-1ra/IL-1 beta ratios, we evaluated polymorphism of the IL-1ra gene and the production of mucosal cytokines in Japanese patients with UC. Colonic biopsy specimens of mucosal tissue were placed in organ cultures for 24 h. Then, the supernatant concentrations of IL-1 beta, IL-1ra, IL-8, IL-4, IL-10, and TGF-beta were assayed by ELISA. Genomic DNA was extracted from patient peripheral blood samples, then IL-1ra gene polymorphism was determined using PCR amplification. The mucosa from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1 beta ratio. In the resolving stage, IL-1ra/IL-1 beta ratios increased with increasing IL-10 and TGF-beta concentrations. The addition of human recombinant IL-10 to the culture supernatants produced concentration-dependent inhibition of IL-1 beta. In Japanese patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1 beta ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory changes.
Ishizuka
K
K
3rd Division, Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan. kisei@med.niigata-u.ac.jp
Sugimura
K
K
Homma
T
T
Matsuzawa
J
J
Mochizuki
T
T
Kobayashi
M
M
Suzuki
K
K
Otsuka
K
K
Tashiro
K
K
Yamaguchi
O
O
Asakura
H
H
D000328:Adult; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000235:genetics*
D016207:Cytokines; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D016753:Interleukin-10