IL-10 is a cytokine with potent anti-inflammatory properties, repressing the expression of inflammatory cytokines such as TNF-alpha, IL-6 and IL-1 by activated macrophages. The IL-10 receptor is in the JAK/STAT class of receptors but activation of the JAK/STAT pathways by IL-10 does not appear on its own to be responsible for the anti-inflammatory properties of this cytokine. The anti-inflammatory actions of IL-10 appear to require induction of the enzyme heme oxygenase-1 (HO-1) through a map kinase pathway involving the p38 kinases. HO-1 is involved in the biosynthesis of heme, and catalyzes a reaction producing carbon monoxide, free iron, and the heme precursor biliverdin. HO-1 is induced by IL-10 and is also induced by oxidative stress. Blocking HO-1 with inhibitors or antisense blocks the anti-inflammatory actions of IL-10. The anti-inflammatory actions of HO-1 appear to be the result of signaling by carbon monoxide it produces since removal of CO blocks the anti-inflammatory action of IL-10 and HO-1. The anti-inflammatory actions of IL-10 may be therapeutically useful either directly or through modulation of HO-1 activity.
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