Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor.
OBJECTIVE
We examined the effects of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) on rat endotoxin-induced uveitis, and to measure the expression of inflammatory cytokines and chemokines with and without the alpha-MSH treatment over the course of the disease.


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 microg of alpha-MSH. The eyes were examined over the next 24 h for inflammation. Aqueous humor was collected 6, 12 and 24 h after endotoxin injections and the number of infiltrating cells were counted in anterior chamber. In addition, we assayed the concentration of protein, nitric oxide, TNF-alpha, IL-6, MCP-1 and MIP-2.


RESULTS
Rats injected with alpha-MSH showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, alpha-MSH-treated rats with endotoxin-induced uveitis (EIU) showed significantly lower concentrations of protein, nitric oxide, proinflammatory cytokines and chemokines in their aqueous humor. Even the early stages of EIU were suppressed by the injection of alpha-MSH.


CONCLUSIONS
Our results demonstrate that the immunosuppressive neuropeptide alpha-MSH inhibits the early induction events of endotoxin-induced inflammation in the eye; therefore, suppresses the subsequent infiltration of cells and intraocular production of inflammatory cytokines and chemokines in eyes. alpha-MSH has a possibility of being a therapeutic strategy for anterior uveitis.
Nishida
Tomomi
T
Department of Ophthalmology, Yokohama City University School of Medicine, 3-9, Fukuura, Kanazawa, Yokohama, Kanagawa 236-0004, Japan. tnishida@med.yokohama-cu.ac.jp
Miyata
Shoji
S
Itoh
Yoshiki
Y
Mizuki
Nobuhisa
N
Ohgami
Kazuhiro
K
Shiratori
Kenji
K
Ilieva
Iliyana Bozhidarova
IB
Ohno
Shigeaki
S
Taylor
Andrew W
AW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001082:Aqueous Humor / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium; D013997:Time Factors; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*; D000521:alpha-MSH / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000521:alpha-MSH