TABLE 12.2.
Important Mediators of the Systemic Inflammatory Response to Endotoxin
| Mediator | Origin | Effects |
|---|---|---|
| TNF | Macrophages | Induces synthesis of TNF, IL-1, IL-6, and GM-CSF |
| Monocytes | Activates neutrophils | |
| Neutrophils | Activates fibrinolysis and coagulation | |
| CD4+ T cells | Activates contact and complement system | |
| Natural killer cells | Induces a catabolic state | |
| Induces insulin resistance | ||
| Is a pyrogen (direct action and via IL-1 induction) | ||
| Induces synthesis of TNF, IL-1, IL-6, PGI2, PAF, and GM-CSF | ||
| IL-1 | Activated macrophages | Activates pyrogen |
| Endothelial cells | Induces malaise | |
| Fibroblasts | Activates neutrophils and chemotaxis | |
| Dendritic cells | Activates fibrinolysis and coagulation | |
| Lymphocytes | Activates contact and complement system | |
| Keratinocytes | Induces acute phase response | |
| Increases activity of lipoprotein lipase | ||
| Mobilizes amino acids | ||
| Induces muscle proteolysis | ||
| IL-6 | Activated macrophages | Induces acute phase response |
| Fibroblasts | Induces stress response | |
| Keratinocytes | Is a weak pyrogen | |
| T lymphocytes | ||
| IL-8 | Macrophages | Activates neutrophils and chemotaxis |
| Endothelial cells | ||
| Thromboxane A2 | Platelets | Induces vasoconstriction |
| Activates platelet aggregation | ||
| PGE2 | Most nucleated cells | Induces vasodilation |
| Activates platelet aggregation | ||
| Induces fever | ||
| PGI2 | Vascular endothelial cells | Induces vasodilation |
| Inhibits platelet aggregation | ||
| PAF | Macrophages | Activates platelet aggregation |
| Platelets | Activates macrophages and neutrophils | |
| Neutrophils | Induces hypotension | |
| Mast cells | Increases vascular permeability | |
| Eosinophils | Aids recruitment of leukocytes | |
| Induces visceral smooth muscle contraction | ||
| Is a negative inotrope and arrhythmogenic | ||
| Induces ileus | ||
| PGF2α | Most nucleated cells | Induces vasoconstriction |
| Activates luteolysis | ||
| Leukotriene B4 | Most nucleated cells | Is a chemoattractant |
| Promotes neutrophil interaction with endothelial cells | ||
| Leukotrienes C4, D4, E4 | Most nucleated cells | Increase vascular permeability |
| Induce bronchoconstriction | ||
| Induce vasoconstriction | ||
| Kinins | Produced from serum precursors | Increase vascular permeability |
| Induce smooth muscle contraction cause pain | ||
| Complement components (C3a, C5a) | Activate neutrophils and chemotaxis | |
| Induce smooth muscle constriction | ||
| Induce mast cell degranulation | ||
| Induce release of histamine and serotonin | ||
| Increase vascular permeability | ||
| Oxygen-derived free radicals | Macrophages | Damage cell membranes |
| Neutrophils | Inactivate enzymes | |
| Damage tissues | ||
| GM-CSF | Induces rebound neutrophilia |
GM-CSF, Granulocyte-monocyte colony-stimulating factor; IL, interleukin; PAF, platelet-activating factor; PG, prostaglandin; TNF, tumor necrosis factor.