title: A new model of induced experimental systemic lupus erythematosus (SLE) in pigs and its amelioration by treatment with a tolerogenic peptide.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, hCDR1, ameliorated lupus manifestations in mice models. The objectives of this study were to induce experimental SLE in pigs and to determine the ability of hCDR1 to immunomodulate the disease manifestations.
  
  
  CONCLUSIONS
  We report here the successful induction, by a monoclonal anti-DNA antibody, of an SLE-like disease in pigs, manifested by autoantibody production and glomerular immune complex deposits. Treatment of pigs with hCDR1 ameliorated the lupus-related manifestations. Furthermore, the treatment downregulated the gene expression of the pathogenic cytokines, interleukin (IL)-1beta, tumor necrosis factor alpha, interferon gamma, and IL-10, and upregulated the expression of the immunosuppressive cytokine transforming growth factor beta, the antiapoptotic molecule Bcl-xL, and the suppressive master gene, Foxp3, hence restoring the expression of the latter to normal levels. Thus, hCDR1 is capable of ameliorating lupus in large animals and is a potential candidate for the treatment of SLE patients.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Sharabi
authors.forename: Molly
authors.initials: M
authors.lastname: Dayan
authors.forename: Heidy
authors.initials: H
authors.lastname: Zinger
authors.forename: Edna
authors.initials: E
authors.lastname: Mozes
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000008:administration & dosage* / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000008:administration & dosage* / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D013552:Swine / Q000276:immunology; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; D022801:Complementarity Determining Regions; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D010446:Peptide Fragments; D051020:bcl-X Protein