Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist.
BACKGROUND
Interleukin 1 (IL-1) is implicated in neuroinflammation, an essential component of neurodegeneration. We evaluated the potential anti-inflammatory effect of a novel peptide antagonist of IL-1 signaling, Ilantide.


METHODS
We investigated the binding of Ilantide to IL-1 receptor type I (IL-1RI) using surface plasmon resonance, the inhibition of Il-1β-induced activation of nuclear factor κB (NF-κB) in HEK-Blue cells that contained an IL-1β-sensitive reporter, the secretion of TNF-α in macrophages, protection against IL-1-induced apoptosis in neonatal pancreatic islets, and the penetration of Ilantide through the blood-brain barrier using competitive enzyme-linked immunosorbent assay (ELISA). We studied the effects of the peptide on social behavior and memory in rat models of lipopolysaccharide (LPS)- and amyloid-induced neuroinflammation, respectively, and its effect in a rat model of experimental autoimmune enchephalomyelitis.


RESULTS
Ilantide bound IL-1RI, inhibited the IL-1β-induced activation of NF-κB, and inhibited the secretion of TNF-α in vitro. Ilantide protected pancreatic islets from apoptosis in vitro and reduced inflammation in an animal model of arthritis. The peptide penetrated the blood-brain barrier. It reduced the deficits in social activity and memory in LPS- and amyloid-treated animals and delayed the development of experimental autoimmune enchephalomyelitis.


CONCLUSIONS
These findings indicate that Ilantide is a novel and potent IL-1RI antagonist that is able to reduce inflammatory damage in the central nervous system and pancreatic islets.
Boris
B
Klementiev
Shizhong
S
Li
Irina
I
Korshunova
Oksana
O
Dmytriyeva
Stanislava
S
Pankratova
Peter S
PS
Walmod
Laura K
LK
Kjær
Mattias S
MS
Dahllöf
Morten
M
Lundh
Dan P
DP
Christensen
Thomas
T
Mandrup-Poulsen
Elisabeth
E
Bock
Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. berezin@sund.ku.dk.
Vladimir
V
Berezin
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C000591539:ilantide