Role of interleukin-1 in the pathogenesis of experimental shigellosis.
The effect of human recombinant interleukin-1 receptor antagonist on intestinal inflammation, tissue destruction, and bacterial invasion during experimental shigellosis caused by Shigella flexneri was studied in 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 intestinal 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 bacterial invasion of their tissues, both at the level of the villous intestine and Peyer's patches. This is conclusive evidence that interleukin-1 plays a critical role in the pathogenesis of shigellosis. This proinflammatory cytokine is here proposed as a major trigger of the inflammatory reaction which is characteristic of this invasive disease of the intestine, due to the particular interaction existing between S. flexneri and macrophages.
Sansonetti
P J
PJ
Unité de Pathogénie Microbienne Moléculaire, Unité 389 Institut National de la Santé et de la Recherche Médicale, Paris, France.
Arondel
J
J
Cavaillon
J M
JM
Huerre
M
M
D000818:Animals; D001284:Atrophy; D004405:Dysentery, Bacillary / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005122:Exudates and Transudates; D006801:Humans; D007249:Inflammation; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007413:Intestinal Mucosa / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages / Q000502:physiology; D009504:Neutrophils; D010477:Perfusion; D010581:Peyer's Patches / Q000276:immunology; D011817:Rabbits; D012763:Shigella flexneri; D012795:Sialoglycoproteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014456:Ulcer / Q000473:pathology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha