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Table 2 Beneficial and detrimental role of inflammatory factors associated with ischemic stroke

From: Neuroinflammation: friend and foe for ischemic stroke

Inflammatory mediators

Produced by

Beneficial

Detrimental

Reference

TNF-α

Macrophages, microglia, neurons

Overexpression of caspases, leukocyte adhesion molecules, and neurotrophic factors enhances endothelial cell dysfunction; modulates extracellular Ca2+ levels and neuronal plasticity; stimulates cerebral microvasculature repair, anti-apoptotic factors, and anti-oxidants; and induce ischemic tolerance

Increases or decreases infarct volume; blocks glutamate uptake, stimulate gliosis and release of neurotoxic mediators; enhance Ca2+ signaling in neurons and apoptosis of endothelial cells, edema formation, BBB disruption, prime endothelium for leukocyte adherence; and upregulate NF-ĸB activation

[65, 283, 284]

IL-6

Macrophages, endothelial cells

Enhances post-stroke angiogenesis associated genes, induction IL-1ra

Endogenous pyrogen, attract T lymphocytes

[285,286,287]

IL-1α/β

Macrophages, microglia, endothelial cells

Enhances IL-1ra expression and promote survival factors

Increases infarct volume, acts as endogenous pyrogen, promote gliosis, increase neurotoxic mediators, enhance Ca2+ in neurons, induce edema formation and BBB disruption, prime endothelium for leukocyte adherence, upregulate MMP-9

[150, 288, 289]

IL-12

Macrophages, TH1 cells

Promote TH1 phenotype

Increases infarct volume

[290, 291, 292]

IL-8

Endothelial cells, macrophages

Neutrophil chemoattractant

Increases infarct volume

[65, 293]

MMPs

Microglia, astrocytes, leukocytes

Helps remove extracellular matrix; stimulates plasticity, recovery, and repair

Clearance necrotic cell debris

Increases infarct volume, excitotoxicity, BBB disruption; promotes leukocyte adherence and transmigration; increases vasogenic edema and hemorrhagic transformation

[20, 294, 295]

iNOS

Endothelial cells, astrocytes, microglia, leukocytes

Promotes vasodilation, key effector molecule of ischemic preconditioning

Increases infarct volume, Induction of iron loss of cells, Inhibition enzymes DNA replication, stimulates expression of inflammatory mediators

[114, 296, 297]

IFN-γ

NK cells, T cells

 

Increases infarct volume, enhances inflammatory chemokine interferon inducible protein 10 (IP-10) and T-cell infiltration

[298, 299]

TGF-β

Astrocytes, microglia,

macrophages

Reduces infarct volume, gliosis, and brain edema; decreases release ROS and apoptosis; prevent neutrophil adherence; Induces IL-1ra expression and angiogenesis, astrocytic TGF-β limit neuroinflammation

Enhance glial scar formation and β-amyloid precursor

[157, 300]

IL-10

Microglia, macrophages, Treg cells, endothelial cells

Decreases infarct volume, diminishes cytokines release and their receptors expression, prevents astrocytic activation, promotes neuronal and glial survival, reduces leukocyte adhesion

 

[301, 302]

HMGB-1

 

Endothelial activation, enhances neuronal survival and neurite outgrowth

Increases infarct volume, vascular permeability, and inflammatory mediators, BBB disruption

Activation of microglia, upregulates NF-ĸB expression

[303, 270, 304]

CINC, MIP-1, MCP-1, fractalkine, MRF-1

Microglia, infiltrating immune cells

Promote neuroblast migration, hematogenous cell recruitment, and functional repair; scavenge and repair necrotic tissue and angiogenesis

Enhance leukocyte and neutrophil infiltration, increase BBB disruption and cerebral edema, stimulate phagocytosis and apoptosis, increase cytokine secretion

[305, 306, 307]

ROS

Neurons, microglia, astrocytes, leukocytes

 

Enhances infarct volume, increased production of ROS, early ROS burst; initiates inflammatory response and lipid peroxidation; disrupts protein biochemistry

[308,309,310]

NO

Neurons, macrophages, astrocytes, microglia, leukocytes, endothelial cells

 

Increases infarct volume, induces protein nitrosylation and iron loss of cells, inhibits enzymes for DNA replication, upregulates inflammatory mediators

[296, 114, 311]