Interleukin 28

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 genes are located near IL-29 on chromosome 19 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. The SNP was identified in a genome-wide association study (GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.

References

References

1. (2004). "Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities". International Journal of Immunopathology and Pharmacology.
2. (January 2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nature Immunology.
3. (June 2009). "Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity". Blood.
4. (September 2010). "IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques". Molecular Therapy.
5. PGxNews.Org. (August 2009). "New biomarker predicts response to hepatitis C treatment". PGxNews.Org.
6. (September 2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature.
7. (June 2011). "Pharmacogenomics: playing the odds". Nature.