Portal de Periódicos da CAPES

Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-γ production from activated B cells

1997; National Academy of Sciences; Volume: 94; Issue: 8 Linguagem: Inglês

10.1073/pnas.94.8.3948

1091-6490

Tomohiro Yoshimoto, Haruki Okamura, Yoh‐ichi Tagawa, Yoichiro Iwakura, Kenji Nakanishi,

Immunotherapy and Immune Responses

Interleukin 18 (IL-18), originally called interferon (IFN)-γ-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-γ 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-γ, 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-γ 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-γ 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-γ-producing cells that inhibit IgE production in them. Furthermore, B cells obtained from normal mice could develop into IFN-γ-producing cells in IFN-γ −/− host mice in response to in vivo treatment with IL-12 and IL-18. These results indicate that IFN-γ 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.