IL-12 is an effective adjuvant for induction of mucosal immunity

We addressed the effects of two cytokines, IL-6 and IL-12, derived from APC s, for the development of mucosal IgA Ab responses following their nasal de livery with the protein vaccine tetanus toroid (TT), Mice treated nasally w ith IL-6 and TT showed higher TT-specific serum IgG (mainly IgG1 and IgG2b) Ab responses than did control mice, but exhibited no IgE and negligible se cretory IgA (S-IgA) Ab responses. In contrast, IL-12 administered nasally w ith TT not only induced sharp increases in TT-specific serum IgG (mainly Ig G1 and IgG2b) and IgA, but also elevated mucosal S-IgA Ab responses, Coadmi nistration of IL-6 and IL-12 with TT did not enhance the mucosal or serum A b responses over those seen with IL-12 alone. TT-specific CD4(+) T cells fr om mice given TT with IL-6 or IL-12 produced higher levels of IFN-gamma, IL -6, and IL-10 than did those from control mice, but only negligible levels of IL-4 and IL-5, In summary, both intranasal IL-6 and IL-12 induced serum Abs that protected mice from systemic challenge with TT, whereas only IL-12 induced mucosal S-IgA Ab responses, The significance of IL-12-induced Th1- type responses for regulation of both mucosal and systemic immunity is disc ussed.