Study note
PathologyInflammation and Repair

TNF and IL-1: production and leukocyte recruitment

THE CONTEXT
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) promote leukocyte adhesion to endothelium and migration through vessels during inflammation.

Cellular sources and stimuli

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Activated macrophages and dendritic cells are the main sources of TNF and IL-1.
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TNF is also produced by T lymphocytes and mast cells; some epithelial cells also produce IL-1.
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Microbial products, necrotic cells, and other inflammatory stimuli can stimulate secretion of both cytokines.

Production and activation

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Signals through TLRs and other microbial sensors induce TNF production and stimulate IL-1 synthesis.
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Generation of biologically active IL-1 additionally depends on activation of the inflammasome.

Endothelial activation

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TNF and IL-1 contribute to local and systemic inflammatory reactions.
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Both increase endothelial expression of adhesion molecules, including E-selectin and P-selectin, supporting leukocyte recruitment.
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