Suppression of endotoxin–induced uveitis (EIU) by alpha–melanocyte–stimulating hormone (–MSH) treatment

Abstract

Abstract: : Purpose: We examined the potential of treating EIU with the neuropeptide α–MSH, which is an important endogenous suppressor of inflammation and immunity. Methods:We injected Lewis rats once with Salmonella typhimurium lipopolysaccharide (LPS) to induce uveitis. The rats were given intravenous injections of 250, 500 or 1000 µg of α–MSH. The eyes were examined over the next 24 hours for inflammation. Also, we assayed aqueous humor collected at 6, 12 and 24 hours after injecting endotoxin and α–MSH for cellular infiltration, and the concentrations of protein, nitric oxide, TNF–alpha, IL–6, MCP–1 and MIP–2. Results:EIU rats treated with α–MSH had significantly suppressed inflammation induced by endotoxin when compared to the untreated EIU rats. Analysis of the aqueous humor from α–MSH treated EIU rats measured a significantly lower cellular infiltration, and concentrations of protein, nitric oxide, cytokines and chemokines. Conclusions:Our results demonstrate that a systemic injection of the immunosuppressive neuropeptide α–MSH inhibits endotoxin–induced uveitis. Also, the α–MSH treatment suppressed endotoxin–induced production of inflammatory cytokines and chemokines in the eye. This is another example of the potential of using our understanding of the mechanisms of immune privilege to treat blinding inflammatory diseases.

Keywords: immunomodulation/immunoregulation • uveitis–clinical/animal model • inflammation