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.
Kuranaga
Noritsugu
N
Department of Immunology and Microbiology, National Defense Medical College, Namiki 3-2, Tokorozawa 359-8513, Japan.
Kinoshita
Manabu
M
Kawabata
Toshinobu
T
Habu
Yoshiko
Y
Shinomiya
Nariyoshi
N
Seki
Shuhji
S
D000818:Animals; D002478:Cells, Cultured; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000096:biosynthesis; D020382:Interleukin-18 / Q000008:administration & dosage / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D018805:Sepsis / Q000276:immunology* / Q000401:mortality; D013156:Splenectomy; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity
D007075:Immunoglobulin M; D020382:Interleukin-18; D007371:Interferon-gamma