Anti-Inflammatory Cytokines: Expression and Action in the Brain

Abstract

Transforming growth factor-β₁ (TGF-β₁) and interleukin (IL)-10 gene expression is equivocal in normal brain and upregulated in over a dozen central and peripheral diseases/disorders. The patterns of specific expression of cytokines differ in these diseases. Published data indicate that these cytokines are produced by and act on both neurons and glial cells. Although their actions are commonly viewed as ‘anti-inflammatory’, they protect neurons and downregulate the responses of glial cells to diseases/disorders in the absence of inflammation. Their actions counterbalance the actions of elevated IL-1 and/or tumor necrosis factor-α to maintain homeostasis. Their therapeutic potential will be realized by improving our understanding of their place in neural cytokine networks.

Role of neuroinflammation in ischemic stroke

“…[110] In the TGF-β superfamily, only TGF-β1, produced by activated microglia, and TGF-β2, produced by astrocytes and neurons. [111] TGF-β1 and TGF-β2 increased prominently after ischemic stroke. After Ischemic stroke, TGF-β produced by activated M2 phenotype macrophage, plays an anti-inflammatory role and contributes to recovery after brain injury.…”

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

“…Furthermore, the CNS was thought to lack of conventional lymphatic drainage. It was reported that a number of anti-inflammatory substances such as TGF-, Fas ligand and ganglioside, which inactivate or kill immune cells (Becher et al, 1998;Benveniste, 1998;Irani, 1998;Bechmann et al, 1999;Gozes et al, 1999;Pender and Rist, 2001;Vitkovic et al, 2001). Increasing reports, however, demonstrate that some degree of immune surveillance of the CNS exists and is crucial to prevent disease development.…”

Driving GDNF expression: The green and the red traffic lights

“…Given the ability of AS101 to protect nigrostriatal dopaminergic neurons in animal models of PD, namely by neurotrophic, anti-apoptotic and anti-inflammatory mechanisms, it was proposed as a promising agent to treat PD (Sredni et al, 2007). Since the effect of IL-10/AS101 does not seem to be cell type-specifically regulated, it may explain the deprivation of neurotrophic factors in several CNS diseases where elevated expression of IL-10 is described (Vitkovic et al, 2001), although the levels of pro-inflammatory agents are usually increased in those diseases. The principal function of IL-10 appears to be limitation and ultimately termination of inflammatory responses (Moore et al, 2001).…”