title: Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model.
abstract: Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.
authors.affiliation: Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: D A C
authors.initials: DA
authors.lastname: Botte
authors.forename: I L
authors.initials: IL
authors.lastname: Noronha
authors.forename: D M A C
authors.initials: DM
authors.lastname: Malheiros
authors.forename: T V
authors.initials: TV
authors.lastname: Peixoto
authors.forename: S B V
authors.initials: SB
authors.lastname: de Mello
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001168:Arthritis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D013729:Terpenes / Q000009:adverse effects; D000521:alpha-MSH / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D000974:Antibodies, Antinuclear; D016207:Cytokines; D007074:Immunoglobulin G; D044102:Receptor, Melanocortin, Type 1; D013729:Terpenes; C009042:pristane; D000521:alpha-MSH; D003346:Corticotropin-Releasing Hormone; D052247:Nitric Oxide Synthase Type II
keywords: arthritis; cytokines; experimental lupus; nephritis; α-MSH