SUPPRESSION OF POLYCLONAL AND ANTIGEN-SPECIFIC MARINE IGG(1) BUT NOT IGE RESPONSES BY NEUTRALIZING INTERLEUKIN-6 IN-VIVO

The crucial role of interleukin (IL)-4 in the induction of murine IgG( 1) and IgE responses,which are coupled through the process of sequenti al isotype switching, has been well documented. Whereas IL-4 is obliga tory for the induction of IgE responses, it enhances IgG(1) responses. In this study, using neutralizing antibodies, we provide evidence tha t, besides IL-4, also IL-6 is required for obtaining peak IgG(1) respo nses. The mRNA levels of these two cytokines are coordinately expresse d in the spleen of mice immunized with trinitrophenol-keyhole limpet h emocyanin (TNP-KLH). No IL-6 requirement was observed for peak IgE res ponses. The IL-6 dependence of IgG(1) responses was found for both ant igen-specific and polyclonal responses. Moreover, it was noted using T NP-KLH and goat anti-mouse (GAM) IgD as antigen that polyclonal IgG(1) responses are more dependent on IL-6 than antigen-specific responses. In vitro experiments revealed that exogenous IL-6 neither enhanced no r inhibited the IgG(1) and IgE production by naive B cells, suggesting that IL-6 did not interfere with the IL-4-induced isotype switch pote ntial. Primary and memory IgG(1) responses were both similarly depende nt on IL-6. These observations point to a role of IL-6 in the terminal differentiation of B cells switched to IgG(1). Neutralization of IL-6 did not inhibit either antigen-specific or polyclonal IgE responses. Therefore, it was concluded that IL-6 is not involved in the terminal differentiation of B cells switched to IgE. These findings thus provid e a distinct role for IL-6, besides IL-4, in regulating murine IgG(1) responses.The formation of IgE, however, is completely dependent on IL -4 alone.