Interleukin-28

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-IL38). 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 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatically assigned a number for its classification (IL-1 to IL-38, status 2017).

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-28 (IL-28) is a cytokine that occurs in 2 isoforms, IL-28A and IL-28B. IL-28 was discovered together with IL-29 only in 2002. The cytokine plays a role in immunological defense reactions against viruses. It is generally assumed that Interleukin-28 belongs to the Interleukin-10 family.

The coding gene is located on chromosome 19 (19 q13.13) (in close proximity to the IL-29 gene). The two isoforms of IL-28 (IL-28A and IL-28B) have a homology of 96%. The IL28B gene codes for human interleukin 28B (interferon-lambda-3, IFNL3).

The receptor for IL-28 is composed of an IL-28-specific alpha chain that couples to the receptor beta chain of IL-10. IL-28 plays a role in the adaptive immune response.

Clinical significance:

In vaccination trials with the lethal H1N1 influenza virus, the addition of IL-28 to the vaccine leads to 100% protection against infection.

It has been shown that the genomic region of the IL28B gene has a prognostic significance for the course and therapeutic response of hepatitis C infection.

In the skin, IL-28 and IL-29 are produced by virus-infected dendritic cells, regulatory T cells (Tregs). In keratinocytes, IL-28 and IL-29 induce growth inhibition. At the same time, these cytokines produce proteins that prevent virus replication. They also induce expression of various receptors such as the toll-like receptor (TLR)3 and the melanoma differentiation associated gene 5.

According to current knowledge, IL-28/IL-29 play an important clearance role in the skin in viral and other microbial infections, probably also in the defence against neoplastic processes.

Furthermore, it was suspected that IL-28 is involved in the pathogenesis of systemic lupus erythematosus.

The "single nucleotide polymorphism" (C/T dimorphism rs12979860) has been associated with therapeutic response in hepatitis C. Homozygous patients with the IL28B-CC genotype have a significantly higher chance of spontaneously eliminating the virus compared to carriers of the CT and TT genotypes. Furthermore, the IL28B-CC genotype shows a significantly better long-term response rate to PEG-IFN-alpha and ribavirin (RBV) combination therapy. The IL28B gene codes for human interleukin 28B (interferon-lambda-3, IFNL3).

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