Overexpression of interleukin-15 protects against Escherichia coli-induced shock accompanied by inhibition of tumor necrosis factor-α-induced apoptosis

Takashi Hiromatsu, Toshiki Yajima, Tetsuya Matsuguchi, Hitoshi Nishimura, Worawidh Wajjwalku, Toshiyuki Arai, Yuji Nimura, Yasunobu Yoshikai

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    43 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1442-1451
    Number of pages10
    JournalJournal of Infectious Diseases
    Volume187
    Issue number9
    DOIs
    Publication statusPublished - May 1 2003

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Infectious Diseases

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