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  • Title: Lethal outcome caused by Porphyromonas gingivalis A7436 in a mouse chamber model is associated with elevated titers of host serum interferon-gamma.
    Author: Huang JH, Lin YY, Lai YY, Hu SW.
    Journal: Oral Microbiol Immunol; 2006 Apr; 21(2):100-6. PubMed ID: 16476019.
    Abstract:
    BACKGROUND/AIMS: Septic shock caused by gram-negative bacteria has been associated with cytokines produced by hosts. Porphyromonas gingivalis A7436, a disseminating strain, caused septic shock-like symptoms and even animal death in a mouse chamber model. However, P. gingivalis exhibits lower endotoxin activities in its lipopolysaccharide than other typical gram-negative bacteria. In this study, we examined the effects of P. gingivalis lethal infection on host pro-inflammatory cytokines production. METHODS: Nude and normal BALB/c mice were infected with a lethal dose of P. gingivalis A7436 using a mouse chamber model. Serum levels of tumor necrosis factor, interleukin (IL)-1beta, IL-12 and interferon-gamma were evaluated. The effects of tumor necrosis factor inhibitor (thalidomide) and anti-interferon-gamma antibody on infection outcomes were examined. RESULTS: All nude mice survived infectious challenge, whereas 100% of normal mice died with abdominal lesions. Bacterial cultures indicated P. gingivalis dissemination to the circulation. Serum levels of tumor necrosis factor, IL-1beta and IL-12 showed no significant differences between nude and normal mice. Thalidomide treatment did not protect normal mice from death but decreased remote lesion occurrence, with concurrent reduced bacterial counts recoverable from blood. There was a 3.5-fold elevation in normal mice serum interferon-gamma titers compared to those of nude mice and anti-interferon-gamma antibody treatment resulted in 100% protection from lethal outcome. CONCLUSION: Lethal outcome following P. gingivalis A7436 infection is T-lymphocyte dependent and involves an increase in systemic interferon-gamma levels. The data further indicate that P. gingivalis transvascular dissemination (bacteremia) alone is not sufficient for lethal outcome.
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