IL10

Synonyms

Interleukin 10, IL-10, IL10, CSIF, Cytokine Synthesis Inhibitory Factor, T-Cell Growth Inhibitory Factor, Interleukin-10, GVHDS, IL10A, TGIF

Description

Interleukin-10 is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene.IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins.Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively.Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3 . In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators . Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha . Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation . In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling.

KO Status

Immunization

Drug Information

Drugs in clinical trials: 7
Latest Research Phase: Phase 3 Clinical

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Thykamine

PUR-0110, PCT-233

Phase 3 Clinical

Purgenesis Technologies

Dermatitis, Colitis, Ulcerative, Proctocolitis

ATX-MS-1467

M-2736, ATX-MS-01, ATX-MS-1467, MSC-2358825A

Phase 2 Clinical

Apitope Technology

Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

BT-063

BT-063

Phase 2 Clinical

Biotest

Lupus Erythematosus, Systemic

KLS-2031

KLS-2031

Phase 2 Clinical

Kolon Life Science

Sciatica, Radiculopathy

Orismilast

LP-0058, LEO-32731

Phase 2 Clinical

Leo Pharma Inc

Drug-Related Side Effects and Adverse Reactions, Psoriasis, Dermatitis, Atopic

MK-1966

MK-1966

Phase 1 Clinical

Merck Sharp & Dohme Corp

Hematologic Neoplasms

Recombinant anti-InE monoclonal antibody

Phase 1 Clinical

Dingfu Biotarget

Solid tumours

HMPL-011

HMPL-011

Pending

Hutchison Medipharma Ltd

Inflammatory Bowel Diseases, Autoimmune Diseases

Recombinant interleukin-10 (psoriasis), National Cancer Institute

rhIL-10

Discontinued

National Cancer Institute

Psoriasis

CC-11006

CC-11006

Discontinued

Celgene Corp

Myelodysplastic Syndromes, Inflammation

References


Title

Authors

Source

Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI

Vieira P., de Waal-Malefyt R., Dang M.-N., Johnson K.E., Kastelein R., Fiorentino D.F., Devries J.E., Roncarolo M.-G., Mosmann T.R., Moore K.W.,

Proc. Natl. Acad. Sci. U.S.A. 88:1172-1176(1991)

Identification of functional domains on human interleukin 10

Gesser B., Leffers H., Jinquan T., Vestergaard C., Kirstein N., Sindet-Pedersen S., Jensen S.L., Thestrup-Pedersen K., Larsen C.G.,

Proc. Natl. Acad. Sci. U.S.A. 94:14620-14625(1997)

Signal peptide prediction based on analysis of experimentally verified cleavage sites

Zhang Z., Henzel W.J.,

Protein Sci. 13:2819-2824(2004)

Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes

de Waal Malefyt R., Abrams J., Bennett B., Figdor C.G., de Vries J.E.,

J. Exp. Med. 174:1209-1220(1991)

Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10

Windsor W.T., Syto R., Tsarbopoulos A., Zhang R., Durkin J., Baldwin S., Paliwal S., Mui P.W., Pramanik B., Trotta P.P.,

Biochemistry 32:8807-8815(1993)

Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes

Willems F., Marchant A., Delville J.P., Gerard C., Delvaux A., Velu T., de Boer M., Goldman M.,

Eur. J. Immunol. 24:1007-1009(1994)

Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed

Frei K., Lins H., Schwerdel C., Fontana A.,

J. Immunol. 152:2720-2728(1994)

IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages

Hashimoto S.I., Komuro I., Yamada M., Akagawa K.S.,

J. Immunol. 167:3619-3625(2001)

Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation

Lin M.T., Storer B., Martin P.J., Tseng L.H., Gooley T., Chen P.J., Hansen J.A.,

N. Engl. J. Med. 349:2201-2210(2003)

Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex

Yoon S.I., Logsdon N.J., Sheikh F., Donnelly R.P., Walter M.R.,

J. Biol. Chem. 281:35088-35096(2006)