title: IL-3 contributes to development of lupus nephritis in MRL/lpr mice.
abstract: MRL/lpr mice develop a spontaneous autoimmune disease that closely resembles human systemic lupus erythematosus (SLE) with DNA autoantibodies, hypergammaglobulinemia, immune complex glomerulonephritis, and systemic vasculitis. Little is known about the role of IL-3 in SLE. In order to study this we analyzed the expression of IL-3 in murine lupus and determined whether blockade of IL-3 with a monoclonal antibody or injection of recombinant IL-3 affects lupus nephritis in MRL/lpr mice. During disease progression IL-3 levels were increased in the plasma and in the supernatant of cultured splenocytes from MRL/lpr mice. Administration of IL-3 aggravated the disease with significantly higher renal activity scores, more renal fibrosis, and more glomerular leukocyte infiltration and IgG deposition. Blockade of IL-3 significantly improved acute and chronic kidney damage, reduced the glomerular infiltration of leukocytes and the glomerular deposition of IgG, and decreased the development of renal fibrosis. Furthermore, DNA autoantibody production, proteinuria, and serum creatinine levels were significantly lower in the anti-IL-3 group. Thus, IL-3 plays an important role in the pathogenesis of SLE and the progression of lupus nephritis. Hence, blockade of IL-3 may represent a new strategy for treatment of lupus nephritis.
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Renner
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Fabian Johannes
authors.initials: FJ
authors.lastname: Hermann
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schmidbauer
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Talke
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez Gomez
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Schiechl
authors.affiliation: Department of Pharmacology and Toxicology, University Regensburg, Regensburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schlossmann
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Hilke
authors.initials: H
authors.lastname: Brühl
authors.affiliation: Medizinische Klinik and Poliklinik IV, Klinikum der LMU München, München, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.|Regensburg Center for Interventional Immunology, University of Regensburg, Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000974:Antibodies, Antinuclear / Q000097:blood; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005355:Fibrosis; D007074:Immunoglobulin G / Q000032:analysis; D007377:Interleukin-3 / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology* / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology; D008181:Lupus Nephritis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D018655:Lymphocyte Count; D051379:Mice; D011507:Proteinuria / Q000209:etiology; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology
chemical_list: D000906:Antibodies; D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007377:Interleukin-3; D003404:Creatinine