The present invention is drawn to fusion proteins comprising a Receptor for Advanced Glycation Endproducts (RAGE) and an immunoglobulin element. The invention also encompasses methods of treating a condition characterized by activation of an inflammatory cytokine cascade comprising administering such fusion proteins. The invention is also drawn to nucleic acids encoding the fusion proteins, as well as vectors and cells comprising such nucleic acids.

In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to a vertebrate high mobility group box (HMGB) polypeptide, methods of detecting and/or identifying an agent that binds to an HMGB polypeptide, methods of treating a condition in a subject characterized by activation of an inflammatory cytokine cascade and methods of detecting an HMGB polypeptide in a sample.