IL-1/IL-1ra balance in the brain revisited - evidence from transgenic mouse models.
The interleukin-1 (IL-1) family is unique in its including an endogenous antagonist of the IL-1 receptor (IL-1ra). IL-1ra has been shown to antagonise IL-1 signalling so effectively, that it came into clinical use within a few years from its discovery. Although barely detectable in the normal brain, IL-1 is dramatically upregulated during neuroinflammation, and also displays peaks of expression in the brain during development, as well as following the induction of long-term potentiation. IL-1 has been ascribed a central role in neuroinflammation accompanying ageing and age-related neurodegenerative conditions. Several experimental models based on genetically modified mice have been used in order to address the role of IL-1 in neurodegeneration and neuroprotection. Most of the findings here are based on the experiments involving a transgenic mouse strain with brain-directed overexpression of human IL-1ra, in which the balance between IL-1 and IL-1ra is permanently tipped towards inhibiting IL-1 signalling. The developmental effects of IL-1 are evident in the altered brain morphology in adult transgenic mice. In addition, IL-1 appears to be central in regulating the elasticity of the brain response to injury. Thus, a number of lines of evidence support the essential role played by IL-1 in development, plasticity, and physiological brain function.
Spulber
S
S
Karolinska Institutet, Dept. of Neurobiology, Care Sciences and Society, Stockholm, Sweden. stefan.spulber@ki.se
Bartfai
T
T
Schultzberg
M
M
D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology; D001923:Brain Chemistry; D016207:Cytokines / Q000502:physiology; D006801:Humans; D055809:Illness Behavior / Q000502:physiology; D007249:Inflammation; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000502:physiology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology; D017472:Receptors, Interleukin-1 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology
D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins