Relationship of interleukin-1 receptor antagonist to mucosal inflammation in inflammatory bowel disease.
Previous work has suggested that the interleukin-1 (IL-1) receptor antagonist, IL-1ra, may regulate mucosal inflammation in inflammatory bowel disease. The present study assessed the relationship of mucosal IL-1ra levels to histologic severity of inflammation and the related proinflammatory cytokines IL-1 beta and IL-6 in children with inflammatory bowel disease. Colonic biopsy specimens from 29 patients with ulcerative colitis, 27 with Crohn's disease, and 24 noninflammatory control subjects were assayed for IL-1ra, IL-1 beta, and IL-6 by enzyme-linked immunosorbent assay. Histologic activity was graded as none, mild, moderate, or severe. Mucosal IL-1 beta levels, but not IL-1ra levels, were significantly elevated in moderate/severely inflamed biopsies from patients with either ulcerative colitis (p < 0.01) or Crohn's disease (p < 0.001) compared with those with none/mild inflammation. The mucosal molar ratio of IL-1ra/IL-1 beta was significantly lower for moderate/severe inflammation compared with none/mild inflammation for patients with ulcerative colitis (p < 0.05) and Crohn's disease (p < 0.01). The mucosal IL-1ra/IL-1 beta ratio was similar in controls to none/mild inflamed biopsies from subjects with either ulcerative colitis or Crohn's disease. Our observations suggest that increasing mucosal inflammation in inflammatory bowel disease in children is associated with a decrease in the "normal" effective IL-1ra/IL-1 beta ratio in which IL-1ra predominates. The importance of this abnormality to the pathogenesis of inflammatory bowel disease awaits further study.
Hyams
J S
JS
Department of Pediatrics, Hartford Hospital, CT 06102-5037, USA.
Fitzgerald
J E
JE
Wyzga
N
N
Muller
R
R
Treem
W R
WR
Justinich
C J
CJ
Kreutzer
D L
DL
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D012795:Sialoglycoproteins / Q000032:analysis / Q000502:physiology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins