IFN-gamma is a master regulator of endotoxin shock syndrome in mice primed with heat-killed Propionibacterium acnes.

Hyper-coagulation, hypothermia, systemic inflammatory responses and shock are major clinical manifestations of endotoxin shock syndrome in human. As previously reported, mice primed with heat-killed Propionibacterium acnes are highly susceptible to the action of LPS to induce tumour necrosis factor (TNF)-alpha and to that of TNF-alpha to trigger lethal shock. Here we investigated the mechanisms underlying the P. acnes-induced sensitization to LPS and TNF-alpha and the development of individual symptoms after subsequent challenge with LPS or TNF-alpha. Propionibacterium acnes-primed wild-type (WT) mice, but not naive mice, exhibited hyper-coagulation with elevated levels of thrombin-antithrombin complexes and anti-fibrinolytic plasminogen activator inhibitor 1 in their plasma, hypothermia, systemic inflammatory responses and high mortality rate after LPS or TNF-alpha challenge. Propionibacterium acnes treatment reportedly induces both T(h)1 and T(h)17 cell development. Propionibacterium acnes-primed Il12p40(-/-) and Ifngamma(-/-) mice, while not Il17A(-/-) mice, evaded all these symptoms/signs upon LPS or TNF-alpha challenge, indicating essential requirement of IL-12-IFN-gamma axis for the sensitization to LPS and TNF-alpha. Furthermore, IFN-gamma blockade just before LPS challenge could prevent P. acnes-primed WT mice from endotoxin shock syndrome. These results demonstrated requirement of IFN-gamma to the development of endotoxin shock and suggested it as a potent therapeutic target for the treatment of septic shock.

[Carcinogenesis in ulcerative colitis-associated colon cancer and surveillance colonoscopy].

It has been widely accepted that long-standing cases with ulcerative colitis, especially pancolitis have higher risk of complicating colitic cancer. Colitic cancer often appears as multi-focal invasive features with un-differentiated histology. Therefore, endoscopic diagnosis of precancerous or cancer associated dysplastic lesions. Surveillance colonoscopy has preventing effects for developing colitic cancer. In western world, annual surveillance colonoscopy with multiple stepwise has been adopted. In Japan, surveillance colonoscopy with targeted biopsies assisted by chromoendoscopy and/or magnifying endoscopy has proven to be efficacious in finding such lesions.