Chemokines and other cytokines in acute inflammation
THE CONTEXT
Chemokines direct leukocyte movement during inflammation and maintain the normal anatomical distribution of cells within tissues.
Chemokine properties and localization
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Chemokines are small proteins of 8–10 kD that act primarily as chemoattractants for specific leukocyte types. About 40 chemokines and 20 chemokine receptors have been identified.
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A cell's expression of chemokine receptors determines which chemokines act on it.
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Chemokines bind proteoglycans, allowing their display at high concentrations on endothelial surfaces and in the extracellular matrix.
Inflammatory and homeostatic functions
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Microbes and other stimuli induce inflammatory chemokine production. Binding to leukocyte receptors stimulates integrin-dependent attachment to endothelium and chemotaxis toward infection or tissue damage.
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Stromal cells constitutively produce some homeostatic chemokines, which localize cells to specific anatomical regions.
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Certain chemokines direct T and B lymphocytes to discrete areas of the spleen and lymph nodes.
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Despite their established inflammatory role, developing antagonists that block chemokine activity has proved difficult.
Other cytokines
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IL-6 is produced by macrophages and other cells and participates in local and systemic reactions.
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IL-17 is produced mainly by T lymphocytes and promotes neutrophil recruitment.
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Antagonists against IL-6 and IL-17 have shown impressive efficacy in treating inflammatory diseases.
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Type I interferons normally inhibit viral replication and also contribute to some systemic manifestations of inflammation.