Interleukin-18 Protects Splenectomized Mice from Lethal Streptococcus pneumoniae Sepsis Independent of Interferon-γ by Inducing IgM Production

摘要

The mechanism of the susceptibility of splenectomized mice to Streptococcus pneumoniae infection and the therapeutic effect of interleukin (IL)–18 were investigated. We demonstrated that, although S. pneumoniae challenge induced IL-12 production, it did not induce either interferon (IFN)–γ or IL-18 production in mice with or without a splenectomy. Liver mononuclear cells stimulated with heat-killed S. pneumoniae but not with viable S. pneumoniae produced IFN-γ in vitro. However, IL-18 pretreatment recovered the low serum immunoglobulin (Ig) M levels in splenectomized mice and completely inhibited mortality after S. pneumoniae infection without any IFN-γ up-regulation. Injection of IgM from noninfected control mice into splenectomized mice before infection confirmed the essential role that IgM plays against S. pneumoniae infection. Therefore, low serum IgM levels but not a low IFN-γ response in splenectomized mice cause lethality in S. pneumoniae infection, and IL-18 pretreatment protects them from infection by increasing IgM levels before infection