IL-10 (Interleukin 10)

IL-10 product center

IL-10 (interleukin 10) was first described in 1989 as cytokine synthesis inhibitory factor, a TH2-derived factor inhibiting the production of IFN-γ and other cytokines in murine TH1 cells. However, in the human system, IL-10 production is not a typical feature of TH2 cells, because both TH1 and TH2 cells are capable of producing IL-10, whereas the main source of T-cell–derived IL-10 is Treg cells.
In the following, we will mainly discuss IL-10 (interleukin 10) & receptor, IL-10 (interleukin 10) function and IL-10 (interleukin 10) therapy.

IL-10 (Interleukin 10) & Receptor

The IL-10 (interleukin 10) gene maps to chromosome 1 both in the human (1q31-32) and murine genomes. Its structure is highly conserved and consists of 5 exons and 4 introns, a trait that is shared by most IL-10 homologs. Human IL-10 is a 37 kDa homodimer consisting of 2 subunits of 178 amino acids long. The IL-10 protein contains 4 conserved cysteine residues in its mature protein sequence and forms 6 α-helices (A-F) in its tertiary structure. The first exon encodes the signal sequence and the A helix, the second exon encodes the AB loop and B helix, the third exon encodes the C and D helices, the fourth exon encodes the DE loop and E helix, and the fifth exon 5 encodes the F helix, the COOH tail, and an untranslated sequence that plays a role in mRNA stability.

IL-10 cellular responses require IL-10 (interleukin 10) receptor on the cell surface. IL-10 receptor consists of two subunits, IL10RA (also known as CD210) and IL10RB, which are all members of the interferon receptor (IFNR) family.

IL-10 (Interleukin 10) Function

IL-10 (interleukin 10), an anti-inflammatory cytokine, suppresses immune function by blocking the synthesis of proinflammatory cytokines (e.g., IL-1, IL-6, IFN-γ, and TNF-α) in T cells, monocytes, and macrophages, and by inhibiting the expression of cell surface molecules involved in antigen presentation and costimulation. These biological functions suggest IL-10 may have utility in the treatment of autoimmune and inflammatory diseases.

IL-10 (Interleukin 10) Therapy

The powerful immunomodulatory properties of IL-10 and the promising results from IL-10 delivery on the course of several inflammatory diseases in experimental models induced the interest on clinical application of IL-10.

To our knowledge, so far, Dekavil is a single-chain V-domain antibody fragment (scFv) of F8, an antibody targeting extra-domain A (EDA) of fibronectin, fused to IL-10 (interleukin 10). It's in phase II clinical trials for the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). It was originally developed by Philogen, then licensed to Pfizer in 2013.

References

1. Akdis, M., Burgler, S., Crameri, R., Eiwegger, T., Fujita, H., Gomez, E., ... & Rhyner, C. (2011). Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. Journal of allergy and clinical immunology, 127(3), 701-721.
2. Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O'Garra, A. (2001). Interleukin-10 and the interleukin-10 receptor. Annual review of immunology, 19(1), 683-765.
3. Josephson, K., Logsdon, N. J., & Walter, M. R. (2001). Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity, 15(1), 35-46.