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'''Interferons''' are signaling proteins that help produce antiviral responses in cells which inhibit viruses from proliferating.<ref name="INF1">{{Cite web | url = http://www.ebi.ac.uk/interpro/entry/IPR000471 | title = Interferon alpha/beta/delta (IPR000471) {{!}} InterPro | last = European Bioinformatics Institute | first = | authorlink = European Bioinformatics Institute | date = |website=|archive-url=|archive-date=|access-date=2019-01-24}}</ref> Interferons are released by cells in response to the presence of [[pathogen]]s such as [[virus]]es, [[bacteria]], parasites, and [[cancer]]ous cells. Interferons are important in the immune response to [[Enterovirus|enteroviruses]]. [[File:Pegasys interferon alpha.png|frameless|380x380px|right|Box of Pegasys interferon alpha for subcutaneous injection.]] ==Types of interferon== ===Interferon type I=== Type I interferons include the [[interferon alpha|interferon alphas]] (IFN-Îą or INF-Îą), [[interferon beta]] (IFN-β or INF-β). Interferon delta (IFN-δ or INF-δ or trophoblast) is also a type I interferon but is not found in humans.<ref name="INF1" /> Excessive, prolonged IFN-I signaling in persistent infections leads to multiple immune dysfunctions. <ref>{{Cite journal | last = Ng | first = Cherie T. | last2 = Snell | first2 = Laura M. | last3 = Brooks | first3 = David G. | last4 = Oldstone | first4 = Michael B.A. | date = 2013-06-12 | title = Networking at the level of host immunity: immune cell interactions during persistent viral infections | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713852/|journal=Cell host & microbe|volume=13|issue=6 | pages = 652â664|doi=10.1016/j.chom.2013.05.014|issn=1931-3128|pmc=3713852|pmid=23768490}}</ref> ===Interferon type II=== [[Interferon gamma]] (IFN-Îł or INF-Îł) is the only member of the type II interferon group found in humans, and is produced by [[Lymphocyte|lymphocytes]], a type of white blood cell. Interferon gamma shows antiviral activity, and helps regulate the immune system.<ref name="INF2">{{Cite web | url = http://www.ebi.ac.uk/interpro/entry/IPR002069?q=interferon | title = Interferon gamma (IPR002069) {{!}} InterPro | last = European Bioinformatics Institute | first = | authorlink = European Bioinformatics Institute | date = | website = ebi.ac.uk|archive-url=|archive-date=|access-date=2019-01-24}}</ref> ===Interferon type III=== [[Interferon lambda]] (IFN-Îť or INF-Îť) is the only member of the recently discovered type III interferon group. In humans the interferon lambda superfamily includes the proteins IFN-lambda1 ([[interleukin 29|IL-29]], interleukin-29), IFN lambda2 ([[interleukin 28A|IL-28A]]), IFN lambda3 ([[interleukin 28B|IL-28B]]) and [[IFNL4]].<ref name="INF3">{{Cite web | url = http://www.ebi.ac.uk/interpro/entry/IPR038326?q=interferon%20type:homologous_superfamily | title = Interferon lambda superfamily (IPR038326) {{!}} InterPro | last = European Bioinformatics Institute | first = | authorlink = | date = | website = European Bioinformatics Institute|language=en|archive-url=|archive-date=|access-date=2019-01-24}}</ref> ==Interferon therapy for ME/CFS== ===Dr Chia's investigation of interferon therapy === Interferon therapy appears to be temporarily very effective for treating enterovirus-associated [[ME/CFS]], with [[Severe and very severe ME|severe bedbound patients]] being able to return to work after treatment, but Dr [[John Chia]] discovered that most patients relapse several months later. However, although Chia found interferon therapy is usually not a long-term solution to ME/CFS, its major short-term efficacy does provide some supporting evidence for the theory that persistent enterovirus infection causes and maintains ME/CFS.<ref name="Chia2005">{{Cite journal | last = Chia | first = J.K.S. | date = 2005-11-01 | title = The role of enterovirus in chronic fatigue syndrome | url = https://jcp.bmj.com/content/58/11/1126|journal=Journal of Clinical Pathology|language=en|volume=58|issue=11|pages=1126â1132|doi=10.1136/jcp.2004.020255|issn=0021-9746|pmid=16254097|quote=The results of antiviral treatment provided supportive evidence for the pathogenic role of RNA in patients with CFS.|via=}}</ref> In Dr Chia's experimental treatments of ME/CFS using interferon, one investigation employed the antiviral drug [[ribavirin]] plus interferon alpha therapy for ME/CFS patients with high titers to [[coxsackievirus B3]] or [[coxsackievirus B5]], resulting in improvements in symptoms, the elimination of enteroviral RNA from [[Peripheral blood mononuclear cell|peripheral blood mononuclear cells]] (PBMC), and a fourfold reduction in coxsackievirus B antibody titers. However, after therapy was complete, relapse typically occurred 4 to 5 months later, along with antibody titers increasing to pretreatment values and the enteroviral RNA returning to the PBMC. In another experiment, interferon alpha plus interferon delta were used in combination to treat severe bedbound ME/CFS patients positive for enteroviral [[RNA]] in their peripheral blood [[Leucocyte|leukocytes]]: 6 out of 11 severe patients were able to return to full or part-time work as a result, but again relapse occurred some month later. Relapse in these interferon-treated patients was often triggered by a bout of heavy exertion. In a further experiment, two severe bedridden ME/CFS patients with enteroviral RNA in their peripheral blood leukocytes were given interferon alpha plus interferon gamma in combination and went into remission, with these improvements lasting for about 14 months before relapsed occurred and their symptoms returned to the pretreatment baseline.<ref name="Chia2005" /><ref name="Chia2014">{{Cite journal | last = Chia | first = John | last2 = Chia | first2 = Andrew | date = 2004 | title = Ribavirin and Interferon-ô° for the Treatment of Patients with Chronic Fatigue Syndrome Associated with Persistent Coxsackievirus B Infection: A Preliminary Observation | url =http://www.jrnlappliedresearch.com/articles/Vol4Iss2/Chia2-Jar-spring.pdf | journal=The Journal of Applied Research|volume=4(2) | pages = 286-292|via=}}</ref> Dr Chia found type 1 interferon does not work for ME/CFS linked to [[coxsackievirus B4]].<ref name="conf">{{Cite web | url = http://www.investinme.org/IIMEC4.shtml | title = Diagnosis and Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Associated with Chronic Enterovirus Infection. Presentation at the Invest in ME International ME Conference, London 2009 (available on DVD). Timecode: 42:31. | last = Chia | first = John | date = 2009 | website = |archive-url=|archive-date=|access-date=|quote=Interestingly enough, my son also has coxsackie B4, and for coxsackie B4, the antibody titer did not change at all, which is what I usually see using ribavirin and interferon; it is ineffective against coxsackie B4.}}</ref> Dr Chia rarely uses interferon now, because he says ME/CFS patients cannot tolerate it.<ref>{{Cite web | url = https://www.youtube.com/watch?v=I44G-tGgLNE&t=3m51s | title = MECFS Alert Episode 39 - Interview with Dr. John Chia, Part 2. Timecode 3:51. | last = Chia | first = John | date = |website=|archive-url=|archive-date=|access-date=|quote=The second thing we use are interferons. This will cost six thousand dollars a month, it is a very harsh treatment to go through. I rarely use it now because people can't tolerate it. I gave it my son twice; he did not like the treatment; he did go into remission for a short time, no more than a few months. Through our experiences we've learned these viruses are hard to get rid of.}}</ref> Chia does sometimes use interferon beta to treat severe bedbound hospitalized patients, as he finds after two weeks treatment, those patients become able to walk around. ===Other studies on interferon therapy for ME/CFS === In a 1993 study, 18 ME/CFS patients were given interferon alpha therapy for 12 weeks, after which patients were observed for a further 3 months. Patients were divided into two groups of 9, one group were treated immediately, and the second group had their treatment delayed for 3 months; none of the second group recovered significantly while waiting for treatment. At the end of the study, 3 out of 18 patients recovered completely, and 2 of these 3 remained well 12 months later. A further 2 patients were improved at the end of the 3 month follow-up period and remained so up to 8 months later. Out of the 5 patients who recovered or improved, 4 had coxsackievirus B IgM antibodies in their serum; but only 1 of the patients who did not improve had coxsackievirus B antibodies, which suggests that interferon therapy works only for enterovirus-associated ME/CFS.<ref name="Brook1993">{{Cite journal | last = Brook | first = M.G. | last2 = Bannister | first2 = B.A. | last3 = Weir | first3 = W.R.C. | date = 1993-09-01 | title = Interferon- Therapy for Patients with Chronic Fatigue Syndrome | url = https://academic.oup.com/jid/article-abstract/168/3/791/870716?redirectedFrom=fulltext|journal=Journal of Infectious Diseases|language=en|volume=168|issue=3 | pages = 791â792|doi=10.1093/infdis/168.3.791|issn=0022-1899}}</ref> In a 1996 study, 30 ME/CFS patients were treated with interferon alpha or placebo in a double-blind crossover trial. The study found that alpha inteferon therapy was particularly effective in the subset of ME/CFS patients who had diminished NK function and normal lymphocyte proliferation.<ref name="See1996">{{Cite journal | last = See | first =D.M. | last2 = Tilles | first2 = J.G. | date = Jan 1996 | title = alpha-Interferon treatment of patients with chronic fatigue syndrome | url = https://www.ncbi.nlm.nih.gov/pubmed/8675231|journal=Immunological Investigations|volume=25|issue=1-2|pages=153â164|issn=0882-0139|pmid=8675231}}</ref> ==Herbs== Several herbs may increase interferon including [[Tulsi]].<ref name="tulsi2011" /> == Learn more == == See also == * [[John Chia]] * [[Enterovirus]] * [[Non-cytolytic enterovirus]] * [[Coxsackie B virus|Coxsackievirus B]] * [[Post-mortem brain studies]] * [[List of enterovirus infection studies]] ==References== <references> <ref name="tulsi2011">{{Cite journal| doi = 10.1016/j.jep.2011.05.012| issn = 1872-7573| volume = 136 | issue = 3| pages = 452â456| last1 = Mondal | first1 = Shankar | authorlink = Shankar Mondal | last2 = Varma | first2 = Saurabh | last3 = Bamola | first3 = Vishwa Deepak | last4 = Naik | first4 = Satya Narayan | last5 = Mirdha | first5 = Bijay Ranjan | last6 = Padhi | first6 = Madan Mohan | last7 = Mehta | first7 = Nalin | last8 = Mahapatra | first8 = Sushil Chandra | title = Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum Linn.) leaf extract on healthy volunteers| journal = Journal of Ethnopharmacology | date = 2011-07-14 | pmid = 21619917}}</ref> </references> [[Category:Body systems]] [[Category:Potential treatments]] [[Category:Immunomodulators]] [[Category:Cytokines]] [[Category:Interferons]]
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