An interleukin-1 binding region oligopeptide from the human type I IL-1 receptor reduces acute inflammation, delayed hypersensitivity reaction, and lethal endotoxemia in animals.
The effect of an interleukin-1 binding region oligopeptide from the interleukin-1 receptor on various inflammatory responses was investigated in animal models. A synthetic peptide (KICIRIQIS) corresponding to 86-93 of the extracellular domain of the human type I interleukin-1 receptor was used. Carrageenan-induced rat paw edema, a model of acute inflammation, was dose dependently suppressed by intraperitoneal administration of the peptide. The delayed hypersensitivity reaction to sheep red cells was diminished by pretreatment of mice with the peptide at a relatively high dose. In a murine lethal endotoxemia model, animals treated with the interleukin-1 receptor peptide (10 mg/kg x 4) showed significantly better survival than vehicle-treated animals when the peptide was administered from 20 minutes after lipopolysaccharide injection. Improved survival was accompanied by suppression of lipopolysaccharide-induced production of colony-stimulating factor, although the peptide did not improve hypoglycemia. These findings suggest that the interleukin-1 receptor peptide may be a potential treatment for various inflammatory processes.
Suzuki
Y
Y
Department of Drug Delivery Systems, St. Marianna University School of Medicine, Kawasaki, Japan.
Tanihara
M
M
Nakagawa
M
M
Furukawa
A
A
Masuda
C
C
Terasawa
K
K
Ichikawa
Y
Y
Mizushima
Y
Y
D000208:Acute Disease; D000818:Animals; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy; D007111:Immunity, Cellular; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000737:chemistry*; D012756:Sheep; D015996:Survival Rate
D003115:Colony-Stimulating Factors; D008070:Lipopolysaccharides; D009842:Oligopeptides; D017472:Receptors, Interleukin-1