Alpha‐melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus‐like model

Summary 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 B alb/c A n 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 (i NOS ), C 3, CD 3, 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 i NOS . Glomerular expression of MCR 1 was reduced in lupus animals. NDP‐MSH treatment reduced arthritis scores by 70% and also diminished I g G 1 and I g G 2a 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 , i NOS 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.