Huang J-H, Lin Y-Y, Lai Y-Y, Hu S-W
Institute of Stomatology, Chung Shan Medical University, Taichung, Taiwan.
Oral Microbiol Immunol. 2006 Apr;21(2):100-6. doi: 10.1111/j.1399-302X.2006.00266.x.
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.
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.
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.
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.
背景/目的：革兰氏阴性菌引起的脓毒症休克与宿主产生的细胞因子有关。牙龈卟啉单胞菌A7436是一种具有播散性的菌株，在小鼠饲养箱模型中可引起脓毒症休克样症状甚至导致动物死亡。然而，牙龈卟啉单胞菌脂多糖中的内毒素活性低于其他典型的革兰氏阴性菌。在本研究中，我们检测了牙龈卟啉单胞菌致死性感染对宿主促炎细胞因子产生的影响。
使用小鼠饲养箱模型，用致死剂量的牙龈卟啉单胞菌A7436感染裸鼠和正常BALB/c小鼠。评估血清中肿瘤坏死因子、白细胞介素（IL）-1β、IL-12和干扰素-γ的水平。检测肿瘤坏死因子抑制剂（沙利度胺）和抗干扰素-γ抗体对感染结果的影响。
所有裸鼠在感染攻击中存活，而100%的正常小鼠死于腹部病变。细菌培养表明牙龈卟啉单胞菌播散至循环系统。裸鼠和正常小鼠血清中肿瘤坏死因子、IL-1β和IL-12水平无显著差异。沙利度胺治疗不能保护正常小鼠免于死亡，但可减少远处病变的发生，同时可使从血液中可回收的细菌数量减少。与裸鼠相比，正常小鼠血清干扰素-γ滴度升高了3.5倍，抗干扰素-γ抗体治疗可使100%的小鼠免于致死结局。
牙龈卟啉单胞菌A7436感染后的致死结局依赖于T淋巴细胞，且涉及全身干扰素-γ水平的升高。数据进一步表明，仅牙龈卟啉单胞菌经血管播散（菌血症）不足以导致致死结局。
