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Interleukin‐1 System in CNS Stress
Author(s) -
BARTFAI TAMAS,
SANCHEZALAVEZ MANUEL,
ANDELLJONSSON SIV,
SCHULTZBERG MARIANNE,
VEZZANI ANNAMARIA,
DANIELSSON ERIK,
CONTI BRUNO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1391.022
Subject(s) - receptor antagonist , proinflammatory cytokine , interleukin 1 receptor antagonist , inflammation , agonist , interleukin , excitatory postsynaptic potential , medicine , neuroscience , antagonist , receptor , pharmacology , cytokine , immunology , biology
Abstract : Proteins of the interleukin‐1 (IL‐1) system include the secreted agonist IL‐1β, and the receptor antagonist IL‐1ra, both competing for binding to the IL‐1 receptor (IL‐1R). IL‐1β and IL‐1ra are highly inducible under different forms of stress, such as excitatory neurotransmitter excess occurring during seizures, in infection and inflammation, and during neurotrauma. In each of these conditions induction of IL‐1β precedes that of IL‐1ra, resulting in up to 10–20‐fold elevation of IL‐1β concentrations. Consequently, IL‐1β induces the elevation of other proinflammatory molecules, including IL‐6, IL‐1R1, COX2, and iNOS, as well as of IL‐1ra. Elevation of IL‐1ra is of key importance for quenching the inflammatory response at the IL‐1R1 as part of an autoregulatory loop. In seizures, IL‐1ra is a strong anticonvulsant and in IL‐1β‐dependent fever, a powerful antipyretic. In traumatic brain injury (TBI), the ability of patients to mount an IL‐1ra response, as measured in the CSF, strongly correlated with the neurological outcome. Selective induction or pharmacological application of IL‐1ra may be sparing neurons in seizures and neurotrauma.