TY - JOUR T1 - Antigen-Specific Suppression of Experimental Autoimmune Encephalomyelitis by a Novel Bifunctional Peptide Inhibitor JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 879 LP - 886 DO - 10.1124/jpet.107.123257 VL - 322 IS - 2 AU - Naoki Kobayashi AU - Hitomi Kobayashi AU - Leo Gu AU - Thomas Malefyt AU - Teruna J. Siahaan Y1 - 2007/08/01 UR - http://jpet.aspetjournals.org/content/322/2/879.abstract N2 - The objective of this study is to evaluate the activity of a novel peptide, i.e., bifunctional peptide inhibitor (BPI), which targets the immunological synapse and inhibits autoimmune responses in an antigen-specific manner. Proteolipid protein (PLP)-BPI was designed by conjugating two peptides, an encephalitogenic epitope of proteolipid protein (PLP139–151) and an intercellular adhesion molecule-1-binding peptide derived from αL integrin (CD11a237–246), via a spacer peptide. The therapeutic effect of PLP-BPI was studied in experimental autoimmune encephalomyelitis (EAE) in female SJL/J mice as a model for human multiple sclerosis. Mice that received i.v. injections of PLP-BPI showed significantly lower EAE disease scores and incidence than those treated with vehicle, PLP139–151 peptide only, CD11a237–246 peptide only, unlinked mixture of PLP139–151, and CD11a237–246 peptides, or other control peptides. Multiple injections of antigenic peptide can produce anaphylactic responses; interestingly, PLP-BPI-treated animals have significantly lower anaphylactic response than do the PLP139–151-treated group. Therefore, PLP-BPI can effectively inhibit the disease severity and incidence of EAE with a lower possibility of inducing fatal anaphylaxis. These results suggest that BPI-type molecules can be used to treat different autoimmune diseases in which antigenic epitopes have been identified. The American Society for Pharmacology and Experimental Therapeutics ER -