Background Alfa-melanocyte stimulating hormone (α-MSH) has a variety of biological functions including reduction of skin delayed-type hypersensitivity, blockage of leukocyte migration, downregulation of pro-inflammatory pathways and inhibition of experimental disease models development including rheumatoid arthritis and inflammatory bowel disease. Nevertheless the anti-inflammatory and immunomodulatory effects of α-MSH on pristane-induced lupus remain unknown.
Objectives To evaluate the effect of a commercial α-MSH analogue (NDP α-MSH)in improving clinical and serological aspects of murine lupus.
Methods Thirty-five BALB/c mice were injected with a single intraperitoneal (IP) dose of 0.5ml pristane for lupus-like model induction and 5 age/gender matched control mice were given saline. Pristane-induced lupus animals received daily IP saline (n=5) or treatments with 3.1mg/kg/d chloroquine (n=10), 1.25mg/kg/d NDP α-MSH (n=10) or 2.5mg/kg/d NDP α-MSH (n=10). Clinical and laboratorial lupus-like parameters were examined before and 180 days after induction, when all animals were sacrificed. Sera ANA was analyzed by IF using Hep2 cells. Mann-Whitney and Fisher test were performed for statistical analysis and P<0,05 considered significant.
Results All lupus-like animals presented large amounts of lipogranulomas in peritoneal cavity, and developed arthritis in both hind legs in contrast to all controls. Of note, lupus animals treated with both doses of α-MSH had important less amounts and smaller lipogranulomas, by visual observation. Mean arthritis score in 5 untreated mice, 9 animals treated with chloroquine and 8 with α-MSH 2.5mg/kg/d was 5.2, 3.33 and 3.1 respectively. Remarkably, mean arthritis score of animals treated with α-MSH 1.25 mg/kg/d was 1.6, significantly lower than untreated mice (1.6 vs 5.2, P=0.0291). Sera ANAs were negative in all 40 animals before pristane lupus injection and 180 days after induction remained negative in normal mice but became positive in all 5 (100%) untreated lupus animals, 7 (77%), 4 (50%) and 3 (35%) of lupus models treated with chloroquine, α-MSH 2.5mg/kg/d and α-MSH 1.25mg/kg/d (100% vs 35%, P=0,0256), respectively. Three animals died before the end of the experiment, by day 150: 1 treated with chloroquine and 2 with higher doses of α-MSH.
Conclusions Improvement of clinical and serological parameters promoted by NDP α-MSH in experimental model of pristane-induced lupus, may suggest a potential role for this drug in human SLE.
Disclosure of Interest None Declared
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