ROLE OF INTERLEUKIN-1 IN THE PATHOGENESIS OF EXPERIMENTAL SHIGELLOSIS

The effect of human recombinant interleukin-1 receptor antagonist on i ntestinal inflammation, tissue destruction, and bacterial invasion dur ing experimental shigellosis caused by Shigella flexneri was studied i n the rabbit-ligated loop infection model, Intravenous infusion of the inhibitor at a dose of 2 mg/kg per h, was initiated 30 min before int estinal loops were ligated and infected, and continued during the 8-h period of infection, The animals treated with IL-1 receptor antagonist showed a striking decrease in inflammation, destruction, and bacteria l invasion of their tissues, both at the level of the villous intestin e and Peyer's patches, This is conclusive evidence that interleukin-1 plays a critical role in the pathogenesis of shigellosis. This proinfl ammatory cytokine is here proposed as a major trigger of the inflammat ory reaction which is characteristic of this invasive disease of the i ntestine, due to the particular interaction existing between S. flexne ri and macrophages.