Tumor necrosis factor (TNF) and interleukin-1 (IL-1) support leukocyte recruitment and activation, produce systemic inflammatory responses, and provide therapeutic targets in chronic inflammation.
Endothelial and cellular activation
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Endothelial changes involving adhesion molecules support leukocyte recruitment. Endothelial activation also increases production of cytokines, chemokines, and eicosanoids and increases procoagulant activity.
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TNF augments neutrophil responses to stimuli such as bacterial endotoxin and stimulates the microbicidal activity of macrophages.
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IL-1 stimulates fibroblasts to synthesize collagen and promotes proliferation of synovial and other mesenchymal cells.
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IL-1 stimulates Th17 responses, which in turn induce acute inflammation.
Systemic responses and cachexia
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IL-1, TNF, and IL-6 induce systemic responses to infection or injury, including fever.
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IL-1 and TNF contribute to systemic inflammatory response syndrome, which may occur with disseminated bacterial infection and other serious conditions.
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At high concentrations, TNF dilates blood vessels and reduces myocardial contractility; both effects contribute to the associated fall in blood pressure.
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TNF promotes lipid and protein mobilization and suppresses appetite. Sustained TNF production contributes to cachexia, characterized by weight loss and anorexia in some chronic infections and cancers.
Therapeutic blockade and its limitations
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TNF antagonists are effective in chronic inflammatory diseases, particularly rheumatoid arthritis, psoriasis, and some forms of inflammatory bowel disease.
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TNF blockade increases susceptibility to mycobacterial infection by reducing the ability of macrophages to kill intracellular microbes.
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IL-1 antagonists are less effective despite overlapping actions of IL-1 and TNF; the reason is unclear.
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Blocking either TNF or IL-1 does not affect the outcome of sepsis, possibly because other cytokines contribute to the systemic reaction.