Role of tumor necrosis factor alpha in gnotobiotic mice infected with an Escherichia coli O157:H7 Strain

Emiko Isogai, Hiroshi Isogai, Koichi Kimura, Shunji Hayashi, Toru Kubota, Nobuhiro Fujii, Koichi Takeshi

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76 Citations (Scopus)


Gnotobiotic mice inoculated with an enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain developed a flaccid paresis, usually culminating in death. The bacteria colonized feces at 109 to 1010 CFU per g (inoculum size: 2.0 x 109 CFU/mouse), and Shiga-like toxins (SLTs) were detected in the feces. A microscopic examination of colons showed mild inflammatory cell infiltration, thinning of the intestinal wall, or necrotic foci. Necrosis of tubular cells was noted in these symptomatic mice. Microhemorrhage, thrombosis, and edematous changes of the brain were also seen. Inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 1α (IL-1α), and IL-6, were detected in the kidney after EHEC infection, but not in the serum. In the brain, only TNF-α was detected. When 2.0 x 102 CFU of EHEC O157:H7 was fed to germ-free mice, the number of bacteria began to rise rapidly on day 1 and was maintained at 108 to 109 CFU/g of feces. SLTs were detected in the feces of the mice. However, the mice showed no histological changes and no cytokine responses, similar to what was found for controls. Treatment with TNF-α modified the clinical neural signs, histopathological changes, and cytokine responses; mice treated with TNF-α developed severe neurotoxic symptoms and had higher frequencies of systemic symptoms and glomerular pathology. Strong cytokine responses were seen in the kidney and brain. Serum cytokines were also detected in this group. In contrast, a TNF- α inhibitor (protease inhibitor) inhibited these responses, especially in the brain. However, local synthesis of the cytokines was observed in the kidney. Thus, TNF-α and the other proinflammatory cytokines could be important in modifying the disease caused by EHEC.

Original languageEnglish
Pages (from-to)197-202
Number of pages6
JournalInfection and immunity
Issue number1
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


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