Interleukin-1 system in CNS stress: seizures, fever, and neurotrauma.
Proteins of the interleukin-1 (IL-1) system include the secreted agonist IL-1beta, and the receptor antagonist IL-1ra, both competing for binding to the IL-1 receptor (IL-1R). IL-1beta 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-1beta precedes that of IL-1ra, resulting in up to 10-20-fold elevation of IL-1beta concentrations. Consequently, IL-1beta 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-1beta-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.
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA. tbartfai@scripps.edu
Tamas
T
Bartfai
Manuel
M
Sanchez-Alavez
Siv
S
Andell-Jonsson
Marianne
M
Schultzberg
Annamaria
A
Vezzani
Erik
E
Danielsson
Bruno
B
Conti
D000818:Animals; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D002490:Central Nervous System / Q000473:pathology* / Q000502:physiology; D004195:Disease Models, Animal; D005334:Fever / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007239:Infections / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000473:pathology*; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000502:physiology; D012640:Seizures / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D018377:Neurotransmitter Agents