Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor (CSIF), is the charter member of the IL-10 family of α-helical cytokines that also includes IL-19, IL-20, IL-22, IL-24, and IL-26/AK155. IL-10 is secreted by many activated hematopoietic cell types as well as hepatic stellate cells, keratinocytes, and placental cytotrophoblasts. Whereas human IL-10 is active on mouse cells, mouse IL-10 does not act on human cells. IL-10 is a 178 amino acid molecule that contains two intrachain disulfide bridges and is expressed as a 36 kDa noncovalently associated homodimer. The IL-10 dimer binds to two IL-10 Rα/IL-10R1 chains, resulting in recruitment of two IL-10 Rβ/IL-10R2 chains and activation of a signaling cascade involving JAK1, TYK2, and STAT3. IL-10Rβ does not bind IL-10 by itself but is required for signal transduction. IL-10 is a critical molecule in the control of viral infections and allergic and autoimmune inflammation. It promotes phagocytic uptake and Th2 responses but suppresses antigen presentation and Th1 proinflammatory responses.