|
| Cytokine/chemokine | Organs/cells upregulated in BD/CNS injury | Stimulation in BD/TBI | Action | Potential therapeutic agents in brain injury |
|
| TNF-α | CNS—astrocytes, microglia, and neurons [70, 118] Endothelial cells [118]
Lungs [119]
Splenocytes, macrophages [6] | Infection, TBI, SAH [118] | Endothelial cell detachment/apoptosis, activation caspase-3, disruption of BBB [118]
Induction of CAM’s, and other inflammatory cytokines [120]
Impairment of cardiac function [121] | IFN-β [119], NNZ-2566 [122], etanercept, and IFN inhibitors [60]
Haemoadsorption [123] |
|
| IL-1β | CNS—neurons, microglia, and infiltrating macrophages [124]
Endothelial cells [118] | Neuroexcitation, infection, and trauma [124]
SAH [118] | Synaptic modulation, central regulation of systemic inflammatory response [124]
Proinflammatory, activation of NFκB and SAPK with upregulation of E-selectin/ICAM/VCAM [118] | IL-1RA [124] and NNZ-2566 [122]
Haemoadsorption [123] |
|
| IL-6 | CNS—microglia [125]
Kidney, liver, spleen, and heart [80, 121, 126–128]
Macrophages [121] | IL-1β [118]
TNF-α [121]
Sepsis, major surgery, heart failure, multitrauma, and burns [80, 84, 127, 129, 130] | Regulator of inflammation—inhibition of TNF and upregulation of control of glial responses and neuronal survival [98–100]
IL-1RA in CNS, induction of NGF [122]
Disruption of BBB [118]
Inducer of acute phase reaction [70, 131]
Cardiac dysfunction, fibroblast activation [127] | Haemoadsorption [123] |
|
| IL-8/CXCL-8/MIP-2 | Microglia [125]
Lung—alveolar macrophages, endothelial cells [132, 133] | Trauma, ischaemia, SAH, ET-1 [118]
TNF-α, IL-1β [120] | Disruption of BBB [118, 120]
CXC chemokine—neutrophil migration and activation [120]
Induces ROS by neutrophils [131] | Haemoadsorption [123] |
|
| IL-10 | Macrophages, microglia [125]
Splenocytes [83]
| TBI [97]
Burns, MT, surgery, and infection [131] | Anti-inflammatory—downregulates TNF-α, IL-1β, and IFN-γ, upregulates antagonists [39, 134]
Reverses effect of proinflammatory cytokines directly on cells [39] | Haemoadsorption [123] |
|
| E-Selectin | Endothelial cells in multiple organs [119] | IL-1β [118] TNF-α [121]
TBI [122]
SAH [118] | Essential for neutrophil rolling, margination, and diapedesis [118] | |
|
| ICAM | Endothelial cells in multiple organs [119] | IL-1β [118] TNF-α [121]
SAH [118] | Essential for neutrophil rolling, margination, and diapedesis [118] | Monoclonal antibodies [118] and IFN-β [119] |
|
| VCAM | Endothelial cells in multiple organs [119] | IL-1β [118] TNF-α [121]
SAH [118] | Essential for neutrophil rolling, margination, and diapedesis [118] | Monoclonal antibodies [118] and IFN-β [119] |
|
| TGF-β | Macrophages, microglia, astrocytes, and neurons [135, 136]
Platelets, choroid epithelium [137] | Constitutively expressed by microglia [134]
SAH [137]
| Anti-inflammatory, may block activation by IL-1β [125]
Regulates T-cell survival and function [136]
Suppresses IFN-γ-induced macrophage upregulation, cytokine and chemokine generation [136]
Downregulation of adhesion molecules [136]
Reduces COX-2 production in microglia [125]
ECM component generation [138]
Angiogenesis [137]
ET-1 generation [139] | Haemoadsorption [123] |
|
| IFN-γ | Microglia [125]
Macrophages [122] | TBI, SAH [122, 125] | Upregulation of CAM’s, chemokines, and innate immune system cells [122] | IFN inhibitors [60] |
|
| COX-2 | CNS—Microglia, endothelial cells [125] | Inflammatory mediators including IL-1β, TNF-α, and IL-6 [125] | Production of prostaglandins, reinforcement of inflammation
[125] | COX inhibitors [125] |
|
