Abstract: Methods for treating anemia in which TNF&agr; activity is detrimental are described.

Abstract: The present invention encompasses a novel approach to develop modified proteins that induce a reduced (or no) immune response (compared to an unmodified protein) in an animal, wherein one or more T cell epitope sequences present in the unmodified protein is/are replaced with one or more “deantigenized” T cell epitope sequences, which exhibit reduced or no binding to a MHC molecule (compared to the T cell epitope); thereby hindering the cellular process of immune response. The present invention provides a novel method for detecting deantigenized T cell epitopes and further reducing or eliminating immunogenicity of an otherwise immunogenic protein by substituting one or more deantigenized T cell epitope sequences for one or more T cell epitope sequences of the parent immunogenic polypeptide.

Abstract: Methods for treating vasculitides in which TNF&agr; activity is detrimental are described.

Abstract: Methods of treating pulmonary disorders comprising administering TNF&agr; inhibitors, including TNF&agr; antibodies are described.

Abstract: Methods of treating TNF&agr;-related disorders comprising administering TNF&agr; inhibitors, including TNF&agr; antibodies are described.

Abstract: Methods for treating coronary disease in which TNF&agr; activity is detrimental are described.

Abstract: The present invention encompasses a novel approach to develop modified proteins that induce a reduced (or no) immune response (compared to an unmodified protein) in an animal, wherein one or more T cell epitope sequences present in the unmodified protein is/are replaced with one or more “deantigenized” T cell epitope sequences, which exhibit reduced or no binding to a MHC molecule (compared to the T cell epitope); thereby hindering the cellular process of immune response. The present invention provides a novel method for detecting deantigenized T cell epitopes and further reducing or eliminating immunogenicity of an otherwise immunogenic protein by substituting one or more deantigenized T cell epitope sequences for one or more T cell epitope sequences of the parent immunogenic polypeptide.

Abstract: A transgenic mouse having somatic and germ cells in which at least one allele of an endogenous interleukin-1.beta. converting enzyme (ICE) gene is functionally disrupted is provided. The mouse may be heterozygous or, more preferably, homozygous for the ICE gene disruption. In homozygous mice, secretion of mature interleukin-1.beta. and interleukin-1.alpha. is substantially reduced relative to non-mutant mice. The mice of the invention can be used as positive controls to evaluate the efficacy of ICE inhibitors and to identify disease conditions that can be treated with ICE inhibitors. A transgenic mouse having functionally disrupted endogenous ICE genes but which has been reconstituted with a human ICE gene is also provided. This mouse can be used to identify agents that inhibit human ICE in vivo.

Abstract: Method for modulating responsiveness to corticosteroids in a subject are provided. In the method of the invention, an agent which antagonizes a factor that regulates production of IFN-.gamma. in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an interferon-.gamma. inducing factor (IGIF) antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders.

Abstract: The present invention provides compositions and methods for the treatment of rheumatoid arthritis in a subject wherein one or more compounds of Formula I as defined herein alone or in combination with one or more other antiarthritic drugs provide suppression of rheumatoid arthritis.

Abstract: The present invention relates to N-substituted derivatives of glutamic acid of pharmaceutical interest, to pharmaceutical compositions which include compounds of the invention and pharmaceutically acceptable carriers, to methods of their preparation, and to their use in purification of interleukin-1.beta. converting enzyme (ICE).

Abstract: The present invention relates to N-substituted derivatives of glutamic acid of pharmaceutical interest, to pharmaceutical compositions which include compounds of the invention and pharmaceutically acceptable carriers, to methods of their preparation, and to their use in purification of interleukin-1.beta. converting enzyme (ICE).