Interleukin 28: Difference between revisions
No edit summary |
No edit summary |
||
| Line 39: | Line 39: | ||
}} | }} | ||
{{SI}} | {{SI}} | ||
{{CMG}} | {{CMG}}; {{AE}} {{VR}} | ||
==Overview== | ==Overview== | ||
Interleukin-28 (IL-28) is a [[cytokine]] that comes in two [[isoform]]s, IL-28A and IL-28B, and plays a role in immune defense against [[virus]]es.<ref>D. | Interleukin-28 (IL-28) is a [[cytokine]] that comes in two [[isoform]]s, IL-28A and IL-28B, and plays a role in immune defense against [[virus]]es.<ref name="Kempuraj-">{{Cite journal | last1 = Kempuraj | first1 = D. | last2 = Donelan | first2 = J. | last3 = Frydas | first3 = S. | last4 = Iezzi | first4 = T. | last5 = Conti | first5 = F. | last6 = Boucher | first6 = W. | last7 = Papadopoulou | first7 = NG. | last8 = Madhappan | first8 = B. | last9 = Letourneau | first9 = L. | title = Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities. | journal = Int J Immunopathol Pharmacol | volume = 17 | issue = 2 | pages = 103-6 | month = | year = | doi = | PMID = 15171810 }}</ref> IL-28A and IL-28B belong to the [[Interferon type III|type III interferon]] family of cytokines and are highly similar (in [[amino acid]] sequence) to [[interleukin 29|IL-29]]. IL-28 [[gene]]s are located near IL-29 on [[chromosome 19]] in humans. | ||
IL-28 [[gene]]s are located near IL-29 on [[chromosome 19]] in humans. | ==Historical Perspective== | ||
IL-28 was discovered in 2003 by Zymogenetics using a genomic screening process in which the entire human genome was scanned for putative genes.<ref name="pmid12469119">{{cite journal | author = Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM | title = IL-28, IL-29 and their class II cytokine receptor IL-28R | journal = Nat. Immunol. | volume = 4 | issue = 1 | pages = 63–8 | year = 2003 | month = January | pmid = 12469119 | doi = 10.1038/ni873 | url = }}</ref> 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]]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. 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 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.<ref name="pmid19304955">{{cite journal | author = Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB | title = Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity | journal = Blood | volume = 113 | issue = 23 | pages = 5868–77 | year = 2009 | month = June | pmid = 19304955 | doi = 10.1182/blood-2008-11-190520 | url = | pmc = 2700323 }}</ref> | |||
== 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.<ref name="pmid19304955" /> 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.<ref name="pmid20571540">{{cite journal | author = Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, Toporovski R, Khan AS, Sardesai NY, Weiner DB. | title = IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques | journal = Molecular Therpay | volume = 18 | issue = 9 | pages = 1714–23 | year = 2010 | month = Sep | pmid = 20571540 | doi = 10.1038/mt.2010.118 | url = | pmc = 2956930 }}</ref> A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to [[hepatitis C]] treatment with [[interferon]] and [[ribavirin]], and high [[LDL]] levels.<ref>{{cite journal |author=Ge D, Fellay j, Thompson A, ''et al.'' |title=Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance |journal=Nature |year=2009 |doi=10.1038/nature08309 |pmid=19684573 |volume=461 |issue=7262 |pages=399–401}}</ref><ref name="Clark-2012">{{Cite journal | last1 = Clark | first1 = PJ. | last2 = Thompson | first2 = AJ. | last3 = Zhu | first3 = M. | last4 = Vock | first4 = DM. | last5 = Zhu | first5 = Q. | last6 = Ge | first6 = D. | last7 = Patel | first7 = K. | last8 = Harrison | first8 = SA. | last9 = Urban | first9 = TJ. | title = Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response. | journal = J Viral Hepat | volume = 19 | issue = 5 | pages = 332-40 | month = May | year = 2012 | doi = 10.1111/j.1365-2893.2011.01553.x | PMID = 22497812 }}</ref> 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.<ref>{{cite journal|last=Maxmen|first=Amy|title=Pharmacogenomics: Playing the odds|journal=Nature|date=NaN undefined NaN|volume=474|issue=7350|pages=S9–S10|doi=10.1038/474S9a|pmid=21666735}}</ref> | |||
== References == | == References == | ||
{{Reflist|2}} | {{Reflist|2}} | ||
{{interleukins}} | {{interleukins}} | ||
Revision as of 20:08, 17 September 2013
| Interleukin 28A | |
|---|---|
| Identifiers | |
| Symbol | IL28A |
| Alt. symbols | , IFNL2 |
| Entrez | 282616 |
| HUGO | 18364 |
| OMIM | 607401 |
| RefSeq | NM_172138 |
| UniProt | Q8IZJ0 |
| Other data | |
| Locus | Chr. 19 q13.13 |
| Interleukin 28B | |
|---|---|
| Identifiers | |
| Symbol | IL28B |
| Alt. symbols | , IFNL3 |
| Entrez | 282617 |
| HUGO | 18365 |
| OMIM | 607402 |
| RefSeq | NM_172139 |
| UniProt | Q8IZI9 |
| Other data | |
| Locus | Chr. 19 q13.13 |
|
WikiDoc Resources for Interleukin 28 |
|
Articles |
|---|
|
Most recent articles on Interleukin 28 Most cited articles on Interleukin 28 |
|
Media |
|
Powerpoint slides on Interleukin 28 |
|
Evidence Based Medicine |
|
Clinical Trials |
|
Ongoing Trials on Interleukin 28 at Clinical Trials.gov Trial results on Interleukin 28 Clinical Trials on Interleukin 28 at Google
|
|
Guidelines / Policies / Govt |
|
US National Guidelines Clearinghouse on Interleukin 28 NICE Guidance on Interleukin 28
|
|
Books |
|
News |
|
Commentary |
|
Definitions |
|
Patient Resources / Community |
|
Patient resources on Interleukin 28 Discussion groups on Interleukin 28 Patient Handouts on Interleukin 28 Directions to Hospitals Treating Interleukin 28 Risk calculators and risk factors for Interleukin 28
|
|
Healthcare Provider Resources |
|
Causes & Risk Factors for Interleukin 28 |
|
Continuing Medical Education (CME) |
|
International |
|
|
|
Business |
|
Experimental / Informatics |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vendhan Ramanujam M.B.B.S [2]
Overview
Interleukin-28 (IL-28) is a cytokine that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against viruses.[1] IL-28A and IL-28B belong to the type III interferon family of cytokines and are highly similar (in amino acid sequence) to IL-29. IL-28 genes are located near IL-29 on chromosome 19 in humans.
Historical Perspective
IL-28 was discovered in 2003 by Zymogenetics using a genomic screening process in which the entire human genome was scanned for putative genes.[2] 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 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.[3]
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.[3] 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.[4] A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to hepatitis C treatment with interferon and ribavirin, and high LDL levels.[5][6] 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.[7]
References
- ↑ Kempuraj, D.; Donelan, J.; Frydas, S.; Iezzi, T.; Conti, F.; Boucher, W.; Papadopoulou, NG.; Madhappan, B.; Letourneau, L. "Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities". Int J Immunopathol Pharmacol. 17 (2): 103–6. PMID 15171810.
- ↑ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM (2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nat. Immunol. 4 (1): 63–8. doi:10.1038/ni873. PMID 12469119. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB (2009). "Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity". Blood. 113 (23): 5868–77. doi:10.1182/blood-2008-11-190520. PMC 2700323. PMID 19304955. Unknown parameter
|month=ignored (help) - ↑ Morrow MP, Yan J, Pankhong P, Shedlock DJ, Lewis MG, Talbott K, Toporovski R, Khan AS, Sardesai NY, Weiner DB. (2010). "IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques". Molecular Therpay. 18 (9): 1714–23. doi:10.1038/mt.2010.118. PMC 2956930. PMID 20571540. Unknown parameter
|month=ignored (help) - ↑ Ge D, Fellay j, Thompson A; et al. (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature. 461 (7262): 399–401. doi:10.1038/nature08309. PMID 19684573.
- ↑ Clark, PJ.; Thompson, AJ.; Zhu, M.; Vock, DM.; Zhu, Q.; Ge, D.; Patel, K.; Harrison, SA.; Urban, TJ. (2012). "Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response". J Viral Hepat. 19 (5): 332–40. doi:10.1111/j.1365-2893.2011.01553.x. PMID 22497812. Unknown parameter
|month=ignored (help) - ↑ Maxmen, Amy (NaN undefined NaN). "Pharmacogenomics: Playing the odds". Nature. 474 (7350): S9–S10. doi:10.1038/474S9a. PMID 21666735. Check date values in:
|date=(help)