Interleukin-18 protects splenectomized mice from lethal Streptococcus pneumoniae sepsis independent of interferon-gamma by inducing IgM production.

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)-gamma 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- gamma 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-gamma 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-gamma response in splenectomized mice cause lethality in S. pneumoniae infection, and IL-18 pretreatment protects them from infection by increasing IgM levels before infection.