Overexpression of interleukin-15 protects against Escherichia coli-induced shock accompanied by inhibition of tumor necrosis factor-alpha-induced apoptosis.
Interleukin (IL)-15, a potent inhibitor of tumor necrosis factor (TNF)-alpha-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-alpha 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-alpha-induced apoptosis in vitro, and neutralization of endogenous IL-15 significantly aggravated TNF-alpha-induced apoptosis. Exogenous IL-15 prevented TNF-alpha-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-alpha-induced apoptosis and protect against E. coli-induced shock, indicating a possible therapeutic application of IL-15 for septic shock.
Hiromatsu
Takashi
T
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan. takasi-h@med.nagoya-u.ac.jp
Yajima
Toshiki
T
Matsuguchi
Tetsuya
T
Nishimura
Hitoshi
H
Wajjwalku
Worawidh
W
Arai
Toshiyuki
T
Nimura
Yuji
Y
Yoshikai
Yasunobu
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology*; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015870:Gene Expression; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012772:Shock, Septic / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D013997:Time Factors; D019076:Transgenes / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha