Interleukin-28 (IL-28) is a

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

that comes in two

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...

s, IL-28A and IL-28B, and plays a role in immune defense against

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...

es, including the induction of an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase as well as ISGF3G (Interferon Stimulated Gene Factor 3). IL-28A and IL-28B belong to the type III interferon family of cytokines and are highly similar (in

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

sequence) to IL-29. Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as opposed to a single exon, as most type-I IFNs are.

Discovery

IL-28 was discovered in 2002 by Zymogenetics using a genomic screening process in which the entire human genome was scanned for putative genes. Once these genes were found, a second scan was performed to look specifically for cytokines. Both IL-28 and IL-29 were found in humans using this type of analysis.

Structure

IL-28

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s are located near IL-29 on

chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 58.6 million base pairs, the building material of DNA. It is considered the most gene-rich chromosom ...

in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous. Differences in function between the two forms remains unclear. The receptor for IL-28 is composed of a unique IL-28 Receptor Alpha chain which pairs with the IL-10 Receptor Beta chain, leading many to classify IL-28 as an IL-10-like family member.

Function

IL-28 has also been shown to play a role in the adaptive immune response, as its inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.

Clinical significance

Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28. Studies of IL-28B in non-human primate models of vaccination confirmed the small animal models, leading to an increase in Interferon Gamma production and CD8+ T cell activity in the form of cytotoxicity in an HIV vaccine study. Scientists have credited this link to explain why some people infected with HSV-1 experience cold sores, while others do not. A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to hepatitis C treatment with interferon and

ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pe ...

. The SNP was identified in a

genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any vari ...

(GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.

References

{{Interleukin receptor modulators Interleukins