Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells.
Interleukin 18 (IL-18), originally called interferon (IFN)-gamma-inducing factor, is a recently cloned cytokine of approximately 18 kDa synthesized by Kupffer cells and activated macrophages. The major activity associated with this molecule is the induction of IFN-gamma production from anti-CD3-activated T helper 1 cells in the presence of IL-12. B cells produce IgG1 and IgE when stimulated with anti-CD40 and IL-4. Here we show that a combination of IL-12 and IL-18 induces anti-CD40-activated B cells to produce IFN-gamma, which inhibits IL-4-dependent IgE and IgG1 production and enhances IgG2a production without inhibiting the B cell proliferative response. We also show that 24.3% of B cells became positive for cytoplasmic IFN-gamma after being stimulated with IL-12 and IL-18. Furthermore, we show that, like splenic T cells stimulated with anti-CD3, IL-12, and IL-18, B cells produced high level of IFN-gamma in response to anti-CD40, IL-12, and IL-18. Injection of a mixture of IL-12 and IL-18 into mice inoculated with Nippostrongylus brasiliensis or injected with anti-IgD induced IFN-gamma-producing cells that inhibit IgE production in them. Furthermore, B cells obtained from normal mice could develop into IFN-gamma-producing cells in IFN-gamma(-/-) host mice in response to in vivo treatment with IL-12 and IL-18. These results indicate that IFN-gamma from activated B cells differentially regulates IgG1/IgE and IgG2a responses in vitro and in vivo, indicating that B cells act as regulatory cells in the immune response. Present results suggested that injection of IL-12 and IL-18 could present a unique approach for the treatment of allergic disorders.
Yoshimoto
T
T
Department of Immunology, Hyogo College of Medicine, Nishinomiya, Japan.
Okamura
H
H
Tagawa
Y I
YI
Iwakura
Y
Y
Nakanishi
K
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004347:Drug Interactions; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma