Interleukin-28 is a cytokine

Cytokine

Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against virus

Virus

A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

es, including the induction an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase

OAS1

2'-5'-oligoadenylate synthetase 1 is an enzyme that in humans is encoded by the OAS1 gene.-Further reading:...

 as well as ISGF3G

ISGF3G

Interferon regulatory factor 9 is a protein that in humans is encoded by the IRF9 gene.-Interactions:ISGF3G has been shown to interact with STAT2 and STAT1....

 (Interferon Stimulated Gene Factor 3). IL-28A and IL-28B belong to the type III interferon

Interferon

Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

 family of cytokines and are highly similar (in amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 sequence) to IL-29

Interleukin 29

Interleukin-29 is a protein that in humans is encoded by the IL29 gene that resides on chromosome 19.IL-29 is a member of the helical cytokine family and is a type III interferon. It is also known as IFNλ1 and is highly similar in amino acid sequence to the IL-28, the other type III interferon...

. 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 2003 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

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s are located near IL-29 on chromosome 19 in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous, although differences in the functions between the two forms remains unclear.

The receptor for IL-28 is composed of a unique IL-28Receptor Alpha chain which pairs with the IL-10Receptor Beta chain, leading many to classify IL-28 as a 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.

A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to hepatitis C

Hepatitis C

Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

 treatment with interferon

Interferon

Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

 and ribavirin

Ribavirin

Ribavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...

. The SNP was identified in a genome-wide association study

Genome-wide association study

In genetic epidemiology, a genome-wide association study , also known as whole genome association study , is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait...

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