Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor (CSIF), is the charter
member of the IL-10 alpha -helical cytokine family that also includes IL-19, IL-20, IL-22, IL-24, and
IL-26/AK155 (1-3). 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 (4, 5). Mature mouse IL-10
shares 85% amino acid sequence identity with rat IL-10 and 70-77% with bovine, canine,
equine, feline, human, ovine, and porcine IL-10. It contains two intrachain disulfide bridges and
is expressed as a 36 kDa noncovalently-associated homodimer (4, 6, 7).
IL-10 mediates its biological activities through a heteromeric receptor complex composed of
the type II cytokine receptor subunits IL-10 R alpha and IL-10 R beta. IL-10 R alpha is a 110 kDa
transmembrane glycoprotein that is expressed on lymphocytes, NK cells, macrophages,
monocytes, astrocytes, intestinal epithelial cells, cytotrophoblasts, and activated hepatic
stellate cells (8-13), while the 75 kDa transmembrane IL-10 R beta is widely expressed (14, 15). The
IL-10 dimer binds to two IL 10 R alpha chains, triggering recruitment of two IL-10 R beta chains (14, 15).
IL-10 R beta does not bind IL-10 directly but is required for signal transduction. IL-10 R beta also
associates with IL-20 R alpha, IL-22 R alpha 1, or IL-28 R alpha to form the receptor complexes for IL-22, IL-26,
IL-28, and IL-29 (16-18).
The involvement of IL-10 in immunoregulation includes both suppressive and stimulatory
effects. It functions as an anti-inflammatory cytokine by inhibiting the expansion and
activation of Th1 cells and Th17 cells (19-21) and by promoting the development of M2
macrophages (21). Its expression by immunosuppressive regulatory T cells (Treg) and
regulatory B cells is important for Treg proliferation (19). Within a tumor microenvironment,
however, IL-10 inhibits the expansion of Treg as well as myeloid-derived suppressor cells
(22, 23). IL-10 induces the intratumoral accumulation and activation of CD8+ T cells (24, 25).
IL-10 exerts protective effects including limiting tissue damage in arthritic inflammation (19)
and promoting muscle regeneration after injury (21), but it also contributes to the persistence
of viral infections (26). The levels of IL-10 are elevated in Sjogren's syndrome (saliva), primary
CNS lymphoma (cerebrospinal fluid), and ovarian cancer (serum and ascites) (27-29). Its levels
are decreased in the serum in patients with recurrent heart attacks or during preeclampsia and
also in the seminal fluid of infertile men (30-32).