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 | |
IL-6 | Macrophages, endothelial cells | Enhances post-stroke angiogenesis associated genes, induction IL-1ra | Endogenous pyrogen, attract T lymphocytes | |
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 | |
IL-12 | Macrophages, TH1 cells | Promote TH1 phenotype | Increases infarct volume | |
IL-8 | Endothelial cells, macrophages | Neutrophil chemoattractant | Increases infarct volume | |
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 | |
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 | |
IFN-γ | NK cells, T cells |  | Increases infarct volume, enhances inflammatory chemokine interferon inducible protein 10 (IP-10) and T-cell infiltration | |
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 | |
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 | Â | |
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 | |
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 | |
ROS | Neurons, microglia, astrocytes, leukocytes | Â | Enhances infarct volume, increased production of ROS, early ROS burst; initiates inflammatory response and lipid peroxidation; disrupts protein biochemistry | |
NO | Neurons, macrophages, astrocytes, microglia, leukocytes, endothelial cells | Â | Increases infarct volume, induces protein nitrosylation and iron loss of cells, inhibits enzymes for DNA replication, upregulates inflammatory mediators |