Interleukin-20

Interleukins (from Latin/Greek inter = between; leukos = white; kinein = to >move) are a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL35). Interleukins are mediators for induction, course and control of T-cell-mediated cytotoxic immune reactions as well as B-cell activation (antibody production). They are mainly formed and secreted by stimulated leukocytes, monocytes and macrophages. So far, about 35 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatically assigned a number for its classification (IL-1 to IL-35).

Some structurally related substances have been grouped into families. Their members often have a similar function or participate in the fine regulation of immune reactions, for example by regulating the synthesis of related interleukins.

Interleukin-20 is a pleiotropic, pro-inflammatory cytokine encoded by the Interleukin-20 gene. Interleukin-20 belongs to the Interleukin-10 family with the members: Interleukin -10, Interleukin -19, Interleukin -22, Interleukin-24, Interleukin -26.

Interleukin-20 is homologous to Interleukin-IL-10 and Interleukin-19, which are organized in a closely coordinated cluster (Interleukin-10 cluster) on chromosome 1q321.

Interleukin-20 is formed and secreted by monocytes, dendritic cells but also keratinocytes. Like interleukin-19, interleukin-20 binds to the interleukin-20 receptor complex and leads to the activation of the "signal transducer and activator of transcription 3" STAT3 signaling pathways.

The Interleukin-10 family comprises multifunctional cytokines with anti-inflammatory properties that consist in the "regulation" of antigen presentation and macrophage activation. Interleukin-10 and Interleukin-19 are immunoregulatory cytokines, while Interleukin-20 is pro-inflammatory. Both receptor units of interleukin-20 are significantly upregulated in psoriatic skin.

Interleukin-20 regulates the proliferation and differentiation of keratinocytes in inflammatory reactions, especially in inflammation of the skin. Interleukin-20 induces the expansion of multipotent hematopoietic cells.

The granulocyte-macrophage colony stimulating factor (GM-CSF) and lipopolysaccharides are able to induce IL 20 expression.

Elevated IL-20 serum levels could be measured in patients with active multiple myeloma as well as in chronic recurrent multifocal osteomyelitis in childhood (CRMO).

In patients with bronchial asthma, mucosal monocytes express increased levels of interleukin-20 .

IL-20 plays a role in the pathophysiology of the Th2 immune response in human bronchial asthma and is considered a potential biomarker of asthma progression.

Interleukin-20 is decreased expressed in the skin of scleroderma patients. This is associated with cutaneous fibrosis and abnormal angiogenesis.

Interleukin 20 is elevated in liver fibrosis, liver cirrhosis and hepatocellular carcinoma.

Anti-IL-20 monoclonal antibodies have been evaluated as potential candidates for the treatment of psoriasis, rheumatoid arthritis, atherosclerosis and osteoporosis. No anti-IL-20 antibodies have been approved to date.

1. Blumberg H et al (2001) Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104: 9-19.
2. Chang C et al (2003) Crystal structure of interleukin-19 defines a new subfamily of helical cytokines. The Journal of Biological Chemistry 278: 3308-3313.
3. Chiu YS et al.(2014) IL-20 and IL-20R1 antibodies protect against liver fibrosis. Hepatology 60:1003-1014. https://www.ncbi.nlm.nih.gov/pubmed/24763901
4. Gallagher G et al. (2000) Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). Genes Immunity 1: 442-450.
5. Hofann SR (2015) Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release.Clin Immunol 161:300-307.