Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells
2009
Abstract Introduction
The melanocortin peptides have marked anti-inflammatory potential, primarily through inhibition of proinflammatory cytokine production and action on phagocytic cell functions. Gout is an acute form of arthritis caused by the deposition of urate crystals, in which phagocytic cells and cytokines play a major pathogenic role. We examined whether alpha-melanocyte-stimulating hormone (?-MSH - Melanotan 2) and its synthetic derivative (CKPV)2 influence urate crystal-induced monocyte (Mo) activation and neutrophil responses in vitro.
Results
The supernatants from MSU crystal-stimulated Mos exerted chemoattractant and priming activity on neutrophils, estimated as ROI production and CD11b membrane expression. The supernatants of Mos stimulated with MSU in the presence of melanocortin peptides had less chemoattractant activity for neutrophils and less ability to prime neutrophils for CD11b membrane expression and oxidative burst. MSU crystal-stimulated Mos produced significant levels of IL-1?, IL-8, TNF-?, and caspase-1. The concentrations of proinflammatory cytokines, but not of caspase-1, were reduced in the supernatants from Mos stimulated by MSU crystals in the presence of melanocortin peptides. Overnight incubation of neutrophils with the peptides significantly inhibited their ability to migrate toward chemotactic supernatants and their capacity to be primed in terms of ROI production.
Conclusions
The present experiments indicate that ?-MSH and (CKPV)2 have a dual effect on MSU crystal-induced inflammation: they prevent Mos from producing neutrophil chemoattractants and activating compounds and inhibit neutrophil responses to these inflammatory substances. These findings agree with the observations of Getting and colleagues, who found that melanocortins had protective action in a rat model of gouty arthritis, and suggest a further mechanism for the protective effect. Our results indicate ?-MSH and related peptides as a potential new class of drugs for the treatment of inflammatory arthritis.
Wow, this is such great news for a lot of patients suffering from Gout! My uncle is one of them and he always complains of pain in his knees, ankles and toes. His treatment will last for about six months. But his vices, alcohol and cigarettes, are still with him. And he will still have the disease as long as he have these vices. I hope Melanotan will be effective for patients like him. Of course nothing beats prevention in the first place, but he is just too stubborn that he won't stop from his addictions.
This is such countless newscast for a lot of patients sorrow from the goat. My brother is one of them and he always protests of discomfort in his laps, ankles and toes. His action will last for about six months. But his immoralities, liquor and rollups, are motionless with him. Then he will still have the disease as long as he have these vices. I hope Melanoma will be actual for patients like him. Of sequence unknown beats deterrence in the first home, but he is just too persistent that he won't stop from his habits.
This is good news for those that suffer from arthritis. This illness is so common and unfortunately, there is no permanent treatment for this. Hopefully, this will advance further to provide better treatment for people who suffer from inflammatory arthritis.
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