title: Novel peptides as potential treatment of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a loss of immunologic tolerance, production of auto-antibodies, and inflammatory damage in multiple organs. We have tested the effect of anti-inflammatory peptide, a H2A histone fragment, termed IIIM1, on MRL/lpr mice, animal model of SLE. Oral administration of IIIM1 at early stage of disease caused reduction in proteinuria and serum anti-dsDNA antibodies. Starting the treatment at advanced stage of disease resulted in prolonged animal survival, decreased lymphadenosis and reduced levels of pathogenic or abnormal double negative CD4(-)CD8(-) cells and B220(+) cells in lymph nodes and spleen. We discovered that IIIM1 induces the production of an additional peptide, a fragment of alpha-1-antitrypsin, termed UBE. A relatively low dose (1 µg/kg) of UBE reduced proteinuria and hematuria in MRL/lpr mice. The beneficial effect of the peptide was corroborated by histological examination. Furthermore a significant reduction in serum IL17, IL12 and anti dsDNA antibodies was observed in the UBE-treated mice. Isolated CD4 cells incubated with the peptide showed a similar cytokine profile. Decreased levels of double negative CD4(-)CD8(-) and B220(+) cells were determined in lymph organs of UBE-treated animals. The beneficial effects of both UBE and IIIM1 suggest these peptides as potential drugs for SLE.
authors.affiliation: Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Shapira
authors.forename: E
authors.initials: E
authors.lastname: Proscura
authors.forename: B
authors.initials: B
authors.lastname: Brodsky
authors.forename: U
authors.initials: U
authors.lastname: Wormser
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D006657:Histones / Q000494:pharmacology / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D006657:Histones; D010446:Peptide Fragments; C560739:UBE peptide, mouse; D000515:alpha 1-Antitrypsin; C530140:lysyl-glycyl-histidyl-tyrosyl-alanyl-glutamyl-arginyl-valyl-glyine