TISSUE INTERLEUKIN-1 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST EXPRESSIONIN ENTEROCOLITIS IN RESISTANT AND SUSCEPTIBLE RATS

Background/Aims: Subserosal injection of purified group A streptococca l peptidoglycan-polysaccharide (PG-APS) induces chronic relapsing gran ulomatous enterocolitis and systemic inflammation in susceptible inbre d Lewis rats but only transient intestinal injury in Buffalo and Fisch er rats. Cecal interleukin 1 (IL-1) and IL-1 receptor antagonist (IL-1 ra) expression was measured in inbred rats displaying differential sus ceptibility to experimental enterocolitis. Methods: The ileum and cecu m of Lewis, Buffalo, and Fischer rats were subserosally injected with purified PG-APS or albumin. IL-1 and IL-1ra messenger RNA (mRNA) and p rotein (IL-1 only) were measured 1 or 27 days later. PG-APS-injected L ewis rats were treated with recombinant human IL-1ra. Kinetics of IL-1 and IL-1ra mRNA expression were studied in peritoneal cells. Results: All rat strains developed acute inflammation with increased cecal con centrations of IL-1beta and IL-1ra mRNA. Lewis rats developed chronic enterocolitis and had higher IL-1 and IL-1ra mRNA tissue levels than B uffalo or Fischer rats, which displayed no chronic inflammation. IL-1b eta and IL-1ra were produced by submucosal granulomas and correlated w ith inflammation. IL-1alpha protein levels paralleled IL-1beta mRNA ex pression. IL-1ra treatment attenuated acute and chronic enterocolitis, adhesions, and arthritis. PG-APS induced IL-1 and IL-1ra expression i n peritoneal cells from Lewis and Fischer rats. Conclusions: Bacterial cell wall polymers stimulate IL-1 and IL-1ra expression in vivo and i n vitro. These counterbalancing cytokines are increased in experimenta l enterocolitis and have important immunoregulatory roles in intestina l inflammation.