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Infection and Immunity, November 1999, p. 6056-6066, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Increased Interleukin-1 (IL-1) and Imbalance between IL-1 and IL-1 Receptor Antagonist during Acute Inflammation in Experimental Shigellosis

Josette Arondel,1 Monique Singer,2 Akihiro Matsukawa,3 Arturo Zychlinsky,4 and Philippe J. Sansonetti1,*

Unité de Pathogénie Microbienne Moléculaire/Unité INSERM 3891 and Unité de Pharmacologie Cellulaire/Unité INSERM 485,2 Institut Pasteur, 75724 Paris Cedex 15, France; Department of Pathology, Kumamoto University Medical School, Kumamoto 860, Japan3; and Department of Microbiology, Skirball Institute, New York University Medical Center, New York, New York 100164

Received 24 March 1999/Returned for modification 11 May 1999/Accepted 5 August 1999

Infection by the enteric bacterial pathogen Shigella results in intense mucosal inflammation and destruction of the colonic and rectal epithelium in infected 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 zones. During the first 4 hours of infection in a rabbit ligated-loop model of intestinal invasion, there are two salient characteristics: (i) a high concentration of IL-1alpha and IL-1beta , both in infected Peyer's patch tissue and in the corresponding efferent mesenteric blood, and (ii) a very low level of expression of IL-1 receptor antagonist (IL-1ra). These may reflect a combination of regulation of expression and secretion of IL-1alpha , IL-1beta , and IL-1ra by both resident and recruited phagocytes and the induction of mononuclear phagocyte apoptosis by Shigella. This low IL-1ra/IL-1 ratio likely accounts for the rapid, uncontrolled inflammation characteristic of shigellosis.

* Corresponding author. Mailing address: Unité de Pathogénie Microbienne Moléculaire/Unité INSERM 389, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33) (0)1 45 68 83 42. Fax: (33) (0)1 45 68 89 53. E-mail: psanson{at}pasteur.fr.

Infection and Immunity, November 1999, p. 6056-6066, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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