title: Histamine ameliorates anti-glomerular basement membrane antibody-induced glomerulonephritis in rats.
abstract: Anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis involves T-helper type 1 (Th1) responses leading to rapid crescent formation. As many inflammatory and immune responses in general are affected by histamine, we examined the effects of histaminergic ligands on immune renal injury in the rat. Female Wistar-Kyoto rats were injected intraperitoneally with an antibody against the GBMs. Histaminergic ligands were then injected twice daily for 5 days after which renal function was assessed by proteinuria. Treatment with histamine led to significant dose-dependent reductions in proteinuria compared to the control antibody-injected group and markedly decreased the number of crescentic glomeruli and macrophage infiltration of the glomeruli. Furthermore, histamine significantly decreased the plasma concentration of interleukin-12, a Th1-type cytokine compared to the antibody-injected control animals. Dimaprit, an H(2)/H(4) agonist, mimicked the effects of histamine on proteinuria and crescent formation. Clozapine, an H(4) agonist, tended to mimic the effects of histamine, whereas an H(1), mepyramine, or an H(2) antagonist, ranitidine, did not reverse the protective effect of histamine. We suggest that histamine may alleviate renal injury in anti-GBM glomerulonephritis by suppressing the immune response.
authors.affiliation: Division of Cardiology and Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kawaramachi Hirokoji, Kyoto 602-8566, Japan. standa@koto.kpu-m.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Tanda
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Sonomura
authors.forename: T
authors.initials: T
authors.lastname: Kusaba
authors.forename: N
authors.initials: N
authors.lastname: Kishimoto
authors.forename: H
authors.initials: H
authors.lastname: Kameyama
authors.forename: K
authors.initials: K
authors.lastname: Tamagaki
authors.forename: M
authors.initials: M
authors.lastname: Okigaki
authors.forename: T
authors.initials: T
authors.lastname: Hatta
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Sado
authors.forename: N
authors.initials: N
authors.lastname: Adachi
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy*; D000906:Antibodies / Q000008:administration & dosage; D001323:Autoantibodies; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D008024:Ligands; D011507:Proteinuria; D051381:Rats
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D008024:Ligands; C051951:antiglomerular basement membrane antibody; D006632:Histamine