Table 7.
Soluble Mediators (Including Cytokines) That Are Activated by Endotoxin
| Description of Mediator | How Endotoxin Initiates Mediator Production | Physiologic Consequences | |
|---|---|---|---|
| Anaphylatoxins C3a and C5a | Cleavage products of C3 and C5 complement | Activates serum complement (classic and alternative pathways) | Vasodilatation, smooth muscle contraction, mononuclear cell and neutrophil chemotaxis, immunomodulation of humoral response |
| Prostaglandins | Cyclooxygenase pathway from arachidonic acid | Activates macrophages and monocytes | Vasodilatation, activate or collaborate with other mediators, modulate macrophage effect on function |
| Leukotrienes | Lipoxygenase pathway from arachidonic acid | Activates macrophages and monocytes | Vasoconstriction, activate or collaborate with other mediators, modulate macrophage effect on function |
| Platelet activating factor (PAF) | Lipid mediators derived from platelets, neutrophils, basophils, mononuclear phagocytes, endothelial cells | Binds to platelets, neutrophils, etc with mediator release | Platelet aggregation, neutrophil degranulation. smooth muscle contraction, increased vascular permeability, hypotension, tissue necrosis, modulate endothelial cell function |
| Tissue factor (TF) | Glycoprotein from monocyte or macrophage cell surfaces | Activates factor XII (intrinsic coagulation pathway), stimulates mononuclear cells (extrinsic coagulation pathway) | Microvascular thrombosis |
| Interleukin 1 (IL-1) | Family of immunoregulator cytokines | Stimulates mononuclear phagocytes and other cells | Fever, lymphocyte activation, coagulation, increases endothelial cell adhesiveness, enhancement of T and B cell immunity, secondarily activate PAF, arachidonic acid products, etc |
| Tumor necrosis factor (cachectin) | Product of activated macrophages | Activates macrophages production | Fever, induces IL-1 from mononuclear and endothelial cells, cytotoxic to tumor cells, amplifies microvascular coagulation |
| Colony-stimulating factor | Heterogeneous glycoproteins from macrophages and B lymphocytes | Induces production by macrophages and B lymphocytes | Stimulates proliferation and differentiation from marrow-derived precursor cells, activates mature macrophages to produce other mediators |
| Gamma-interferon | Lymphokine from activated T lymphocytes | Complex pathwaya (see ref 40) | Increases antibacterial and anti-tumor activity of macrophages increases expression of Fc receptors, augments other immune responses, amplifies endotoxin effects (?vicious cycle) |
| Endorphins | Endogenous opioids | Unknown, could stimulate mononuclear cells | Hypotension, analgesia, behavior changes, immune regulation (enhancing and suppressing) |
a
Alpha and beta interferon are induced by endotoxin directly from B lymphocytes and macrophages.
From Morrison. Ryan.28