Abstract: The present invention provides the molecular basis for cytokine induction of NF-&kgr;B-dependent immune and inflammatory responses, emphasizing a role for both NIK-NIK and NIK-IKK protein—protein interactions. A relatively small region of NIK selectively impairs the NIK-IKK interaction. The present invention provides a novel and highly specific method for modulating NF-&kgr;B-dependent immune, inflammatory, and anti-apoptotic responses, based on interruption of the critical protein—protein interaction of NIK and IKK. The present invention provides methods for inhibiting NF-&kgr;B-dependent gene expression, using mutant NIK proteins. One embodiment of the present invention provides kinase-deficient NIK mutant proteins that inhibit activation of IKK. Another embodiment of the invention provides N-terminus NIK mutant proteins that bind IKK, thus inhibiting NIK/IKK interaction.

Abstract: The in vivo effect of Type I interferon (IFN) can be prolonged by administering the interferon in the form of a complex with an IFN binding chain of the human interferon &agr;/&bgr; receptor (IFNAR). Such a complex also improves the stability of the IFN and enhances the potency of the IFN. The complex may be a non-covalent complex or one in which the IFN and the IFNAR are bound by a covalent bond or a peptide. When bound by a peptide bond in the form of a fusion protein, the IFN may be separated from the IFNAR by means of a peptide linker. Such a fusion protein may be produced by recombinant DNA technology. Storing IFN in the form of such a complex improves the storage life of the IFN and permits storage under milder conditions than would otherwise be possible.

Abstract: A method for stimulating host defense mechanisms in a mammal via administering to the mammal a therapeutically effective amount of an interferon via oromucosal contact. The amount of interferon administered is less than an amount which induces a pathological response when administered parenterally.