-
Views
-
Cite
Cite
Takashi Hiromatsu, Toshiki Yajima, Tetsuya Matsuguchi, Hitoshi Nishimura, Worawidh Wajjwalku, Toshiyuki Arai, Yuji Nimura, Yasunobu Yoshikai, Overexpression of Interleukin-15 Protects against Escherichia coli-Induced Shock Accompanied by Inhibition of Tumor Necrosis Factor-α-Induced Apoptosis, The Journal of Infectious Diseases, Volume 187, Issue 9, 1 May 2003, Pages 1442–1451, https://doi.org/10.1086/374643
- Share Icon Share
Abstract
Interleukin (IL)-15, a potent inhibitor of tumor necrosis factor (TNF)-α-mediated apoptosis, causes multiple organ failure during endotoxic shock. We investigated the potential role of IL-15 in protection against Escherichia coli-induced shock by using IL-15 transgenic (Tg) mice. These mice were resistant to an otherwise lethal challenge with E. coli although bacterial burden and serum levels of TNF-α were similar in non-Tg mice. Apoptosis in cells of the peritoneal cavity, liver, spleen, or lung was significantly suppressed in IL-15 Tg mice after E. coli infection. Peritoneal cells from naive IL-15 Tg mice were also resistant to TNF-α-induced apoptosis in vitro, and neutralization of endogenous IL-15 significantly aggravated TNF-α-induced apoptosis. Exogenous IL-15 prevented TNF-α-induced apoptosis in normal mice in vitro and improved the survival rate after E. coli challenge. These results suggest that IL-15 overexpression can prevent TNF-α-induced apoptosis and protect against E. coli-induced shock, indicating a possible therapeutic application of IL-15 for septic shock