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Tissue interleukin 1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats.

AbstractBACKGROUND/AIMS:
Subserosal injection of purified group A streptococcal peptidoglycan-polysaccharide (PG-APS) induces chronic relapsing granulomatous enterocolitis and systemic inflammation in susceptible inbred Lewis rats but only transient intestinal injury in Buffalo and Fischer rats. Cecal interleukin 1 (IL-1) and IL-1 receptor antagonist (IL-1ra) expression was measured in inbred rats displaying differential susceptibility to experimental enterocolitis.
METHODS:
The ileum and cecum of Lewis, Buffalo, and Fischer rats were subserosally injected with purified PG-APS or albumin. IL-1 and IL-1ra messenger RNA (mRNA) and protein (IL-1 only) were measured 1 or 27 days later. PG-APS-injected Lewis rats were treated with recombinant human IL-1ra. Kinetics of IL-1 and IL-1ra mRNA expression were studied in peritoneal cells.
RESULTS:
All rats strains developed acute inflammation with increased cecal concentrations of IL-1 beta and IL-1ra mRNA. Lewis rats developed chronic enterocolitis and had higher IL-1 and IL-1ra mRNA tissue levels than Buffalo or Fischer rats, which displayed no chronic inflammation. IL-1 beta and IL-1ra were produced by submucosal granulomas and correlated with inflammation. IL-1 alpha protein levels paralleled IL-1 beta mRNA expression. IL-1ra treatment attenuated acute and chronic enterocolitis, adhesions, and arthritis. PG-APS induced IL-1 and IL-1ra expression in peritoneal cells from Lewis and Fischer rats.
CONCLUSIONS:
Bacterial cell wall polymers stimulate IL-1 and IL-1ra expression in vivo and in vitro. These counterbalancing cytokines are increased in experimental enterocolitis and have important immunoregulatory roles in intestinal inflammation.
AuthorsR D McCall, S Haskill, E M Zimmermann, P K Lund, R C Thompson, R B Sartor
JournalGastroenterology (Gastroenterology) Vol. 106 Issue 4 Pg. 960-72 (Apr 1994) ISSN: 0016-5085 [Print] United States
PMID8144001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Interleukin-1
  • Polysaccharides, Bacterial
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • streptococcal polysaccharide group A
Topics
  • Animals
  • Cecum (metabolism)
  • Enterocolitis (genetics, metabolism, pathology)
  • Female
  • Genetic Predisposition to Disease
  • Interleukin-1 (genetics, metabolism)
  • Macrophages, Peritoneal (drug effects)
  • Polysaccharides, Bacterial (pharmacology)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Inbred BUF
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Receptors, Interleukin-1 (antagonists & inhibitors, genetics)
  • Recombinant Proteins
  • Streptococcus pyogenes

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