The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective

Abstract

Elevation of the proinflammatory cytokine Interleukin-1 (IL-1) is an integral part of the local tissue reaction to central nervous system (CNS) insult. The discovery of increased IL-1 levels in patients following acute injury and in chronic neurodegenerative disease laid the foundation for two decades of research that has provided important details regarding IL-1's biology and function in the CNS. IL-1 elevation is now recognized as a critical component of the brain's patterned response to insults, termed neuroinflammation, and of leukocyte recruitment to the CNS. These processes are believed to underlie IL-1's function in the setting of acute brain injury, where it has been ascribed potential roles in repair as well as in exacerbation of damage. Explorations of IL-1's role in chronic neurodegenerative disease have mainly focused on Alzheimer disease (AD), where indirect evidence has implicated it in disease pathogenesis. However, recent observations in animal models challenge earlier assumptions that IL-1 elevation and resulting neuroinflammatory processes play a purely detrimental role in AD, and prompt a need for new characterizations of IL-1 function. Potentially adaptive functions of IL-1 elevation in AD warrant further mechanistic studies, and provide evidence that enhancement of these effects may help to alleviate the pathologic burden of disease.

cFLIP is critical for oligodendrocyte protection from inflammation

“…Exposure to Cre recombinase induces IL-1β expression, reaching peak inflammation at 14 days. [45][46][47] We further confirmed that intracranial injection of Cre recombinase-expressing lentivirus caused upregulation of a number of inflammatory markers, including IFNγ and TNFα (Figure 7d). …”

“…IL-1β XAT mice show no overt oligodendrocyte death despite significant leukocyte infiltration into the CNS, [45][46][47] suggesting Figure 4 PKR activation is required for IFNγ-mediated oligodendrocyte protection. (a) Whole-cell lysates were obtained from oligodendrocytes treated as indicated for 72 h and probed by western blotting for PKR, phospho-eIF2α, eIF2α, phospho-PERK, PERK and β-tubulin.…”

Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation

“…Interleukin-1-beta (IL-1β), a critical component of brain neuroinflammation, is increased in AD brains 5 and may contribute to AD pathology by increasing amyloid precursor protein (APP) gene expression, Tau hyperphosphorylation and memory impairment. 6 However, antiinflammatory therapies have not provided the expected beneficial effect in AD patients, 7 suggesting that microglial inflammation may be a consequence of AD. Degenerating neurons are renowned initiators of brain inflammatory responses and the loss of synapses remains the best correlative marker of dementia in AD.…”

Evaluation of an α synuclein sensitized dendritic cell based vaccine in a transgenic mouse model of Parkinson disease

“…[37][38][39] As such, IL-1a levels in brain lysates, prepared as indicated above, were measured in the non-Tg WT as well as experimental and control vaccinated a¡Syn expressing Tg mice. Data on levels of IL-1a are indicated in Figure 4 and are expressed as mean pg/ml brain lysate § SEM.…”