Interleukin‐1: A master regulator of neuroinflammation

Abstract

Interleukins 1alpha and 1beta (IL-1) are very potent signaling molecules that are expressed normally at low levels, but are induced rapidly in response to local or peripheral insults. IL-1 coordinates systemic host defense responses to pathogens and to injury and not surprisingly it has similar effects within the central nervous system (CNS). Numerous reports have correlated the presence of IL-1 in the injured or diseased brain, and its effects on neurons and nonneuronal cells in the CNS, but it is only recently that the importance of IL-1 signaling has been recognized. This article reviews studies that demonstrate that IL-1 is at or near the top of the hierarchical cytokine signaling cascade in the CNS that results in the activation of endogenous microglia and vascular endothelial cells to recruit peripheral leukocytes (i.e., neuroinflammation). The IL-1 system thus provides an attractive target for therapeutic intervention to ameliorate the destructive consequences of neuroinflammation.

Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism

“…4D). Since it is well known that TNF-a [32] and IL-1b [33] as well as IFN-c are produced from microglia or invaded immune cells at the inflammatory lesions, we next examined the effect of TNF-a and IL1b, alone or in combination, on the expression of MHC class I by HB1.F3 cells. As shown in Fig.…”

Non-muscle Mlck is required for β-catenin- and FoxO1-dependent downregulation of Cldn5 in IL-1β-mediated barrier dysfunction in brain endothelial cells

“…Several lines of evidence from animal studies have supported a role for IL-1b in BBB dysfunction during neuroinflammation: (1) IL-1b concentrations are elevated concomitantly with BBB hyperpermeability in animal models of neuroinflammation (Basu et al, 2004;Chakraborty et al, 2010;Simi et al, 2007); (2) injecting recombinant IL-1b induces BBB hyperpermeability (Blamire et al, 2000;Quagliarello et al, 1991); and (3) IL-1b receptor antagonists, or genetic deletion of the IL-1 receptor, attenuate BBB hyperpermeability that is induced by neuroinflammation (Lazovic et al, 2005;Yamasaki et al, 1995). Furthermore, evidence for IL-1b mediating BBB hyperpermeability is also reinforced by in vitro experiments that demonstrate a direct effect of IL-1b in the induction of BBB dysfunction (Didier et al, 2003).…”

The Tryptophan Metabolite 3-Hydroxyanthranilic Acid Plays Anti-Inflammatory and Neuroprotective Roles During Inflammation

“…17,20 Microglial response to a number of brain insults could also promote injury by establishing a cytokine cascade in the CNS through positive feedback mechanisms (IL-1 induces itself) and activation of astrocytes. [21][22][23][24][25] IL-1 is required for human astrocyte inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-␣ release 26 and is critical for neurotoxicity. [27][28][29] The prolonged presence of proinflammatory cytokines, such as IL-1 or TNF-␣, could comprise a common mechanism underlying neurodegeneration.…”