Tissue interleukin 1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats.
OBJECTIVE
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.
McCall
R D
RD
Department of Internal Medicine, University of North Carolina at Chapel Hill.
Haskill
S
S
Zimmermann
E M
EM
Lund
P K
PK
Thompson
R C
RC
Sartor
R B
RB
D000818:Animals; D002432:Cecum / Q000378:metabolism; D004760:Enterocolitis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D011994:Recombinant Proteins; D013297:Streptococcus pyogenes
D007375:Interleukin-1; D011135:Polysaccharides, Bacterial; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; C036112:streptococcal polysaccharide group A