Multiple interleukin-18 injections promote both mouse Th1 and Th2 responses after sublethal Escherichia coli infection.
Interleukin (IL)-18 is considered to induce exclusively the Th1 immune response but not the Th2 response in the presence of adequate IL-12 stimulation in bacterial infections. However, we demonstrate herein that multiple IL-18 injections to the mice not only enhance the early Th1 response but also stimulate the Th2 response later after viable Escherichia coli infection. Multiple IL-18 injections (three alternate-day injections) raised the serum interferon (IFN)-gamma level at 6 h and serum Th2 cytokine levels, such as IL-4, IL-10 and IL-13, at 48 h after infection, while a single IL-18 injection increased only the serum IFN-gamma level. Depletion of mouse CD4+ cells suppressed the IL-18-induced Th2 cytokines, IL-4, IL-10 and IL-13. In contrast, depletion of natural killer (NK)1.1+ cells reduced the IFN-gamma and IL-13 levels. Moreover, multiple IL-18 injections up-regulated the serum IgM level at 72 h after infection while a single IL-18 injection did not. Interestingly, neutralization of IL-4 but not IFN-gamma partially suppressed the increased serum IgM. Liver mononuclear cells (MNCs) from the mice treated with multiple IL-18 injections significantly increased more production of not only IFN-gamma but also Th2 cytokines and IgM by in vitro lipopolysaccharide (LPS) stimulation than those from the phosphate-buffered saline (PBS)-treated mice, while liver MNCs from the single IL-18-injected mice also increased IFN-gamma production but significantly suppressed IL-4 and IgM production compared to those from the PBS-treated mice. Our findings suggest that multiple injections of IL-18 up-regulate both the cellular and humoral innate immunities, thereby enhancing host defence against bacterial infections.
Kinoshita
M
M
Division of Basic Traumatology, National Defense Medical College, Namiki, Tokorozawa, Japan.
Kuranaga
N
N
Matsumoto
A
A
Ono
S
S
Shinomiya
N
N
Hiraide
H
H
Seki
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation; D016207:Cytokines / Q000097:blood*; D004334:Drug Administration Schedule; D004927:Escherichia coli Infections / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D020382:Interleukin-18 / Q000008:administration & dosage*; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007075:Immunoglobulin M; D018793:Interleukin-13; D020382:Interleukin-18; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma