Format

Send to

Choose Destination
Infect Immun. 2010 Sep;78(9):3689-99. doi: 10.1128/IAI.00616-10. Epub 2010 Jul 6.

Role of tumor necrosis factor alpha in disease using a mouse model of Shiga toxin-mediated renal damage.

Author information

1
Department of Microbial and Molecular Pathogenesis, 407 Reynolds Medical Building, Texas A&M University Health Science Center, College Station, TX 77843-1114, USA.

Abstract

Mice have been extensively employed as an animal model of renal damage caused by Shiga toxins. In this study, we examined the role of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) in the development of toxin-mediated renal disease in mice. Mice pretreated with TNF-alpha and challenged with Shiga toxin type 1 (Stx1) showed increased survival compared to that of mice treated with Stx1 alone. Conversely, mice treated with Stx1 before TNF-alpha administration succumbed more quickly than mice given Stx1 alone. Increased lethality in mice treated with Stx1 followed by TNF-alpha was associated with evidence of glomerular damage and the loss of renal function. No differences in renal histopathology were noted between animals treated with Stx1 alone and the TNF-alpha pretreatment group, although we noted a sparing of renal function when TNF-alpha was administered before toxin. Compared to that of treatment with Stx1 alone, treatment with TNF-alpha after toxin altered the renal cytokine profile so that the expression of proinflammatory cytokines TNF-alpha and interleukin-1beta (IL-1beta) increased, and the expression of the anti-inflammatory cytokine IL-10 decreased. Increased lethality in mice treated with Stx1 followed by TNF-alpha was associated with higher numbers of dUTP-biotin nick end labeling-positive renal tubule cells, suggesting that increased lethality involved enhanced apoptosis. These data suggest that the early administration of TNF-alpha is a candidate interventional strategy blocking disease progression, while TNF-alpha production after intoxication exacerbates disease.

PMID:
20605983
PMCID:
PMC2937432
DOI:
10.1128/IAI.00616-10
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center