Increased interleukin-1 (IL-1) and imbalance between IL-1 and IL-1 receptor antagonist during acute inflammation in experimental shigellosis

Infection by the enteric bacterial pathogen Shigella results in intense muc osal inflammation and destruction of the colonic and rectal epithelium in i nfected humans. Initial bacterial translocation occurs through the follicle -associated epithelium, Previous experiments suggest that interleukin-1 (IL -1) is crucial to trigger inflammation, particularly in the follicular zone s. During the first 4 hours of infection in a rabbit ligated-loop model of intestinal invasion, there are two salient characteristics: (i) a high conc entration of IL-1 alpha and IL-1 beta, both in infected Peyer's patch tissu e and in the corresponding efferent mesenteric blood, and (ii) a very low l evel of expression of IL-1 receptor antagonist (IL-1ra). These may reflect a combination of regulation of expression and secretion of IL-1 alpha, IL-1 beta, and IL-1ra by both resident and recruited phagocytes and the inducti on of mononuclear phagocyte apoptosis by Shigella, This low IL-1ra/IL-1 rat io likely accounts for the rapid, uncontrolled inflammation characteristic of shigellosis.