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

Gastroenterology. 1994 Apr;106(4):960-72. doi: 10.1016/0016-5085(94)90755-2.


Background/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cecum / metabolism
  • Enterocolitis / genetics*
  • Enterocolitis / metabolism*
  • Enterocolitis / pathology
  • Female
  • Genetic Predisposition to Disease
  • Interleukin-1 / genetics
  • Interleukin-1 / 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*
  • Receptors, Interleukin-1 / genetics
  • Recombinant Proteins
  • Streptococcus pyogenes


  • Interleukin-1
  • Polysaccharides, Bacterial
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • streptococcal polysaccharide group A