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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,
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]