Interferon gamma (IFN-γ): functions, increased and decreased levels, methods of normalization

IFN-gamma (interferon gamma) is an essential immune protein for the immune response against infectious bacteria, viruses and fungi. Learn more about normal ranges and how to increase or decrease them.

The article is based on the findings of 112 scientific studies

The article quotes authors such as:

Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California, USA
University of New South Wales, Biotechnology and Biomedical Sciences, Sydney, Australia
Department of Dermatology, University of Colorado School of Medicine, USA

Attention! All articles on the site are for informational purposes only. Before using any techniques or recommendations, be sure to consult with your doctor or specialist .

What is interferon gamma (IFN-γ, IFN-gamma)?

Interferon gamma (IFN-γ) is a cytokine critical to both innate and adaptive immunity and functions as a major activator of macrophages, in addition to stimulating NK natural killer cells and neutrophils. Mainly secreted by activated immune T cells and natural killer NK cells.

IFN-gamma (IFN-γ or type II interferon) is an immune protein. It is essential for the body's immune response against fungal, bacterial and viral infections. It controls genes responsible for immune and inflammatory responses and activates macrophages, natural killer NK cells and neutrophils. ()

Interferon gamma is the main activator of macrophages, mainly through the induction of superoxide, nitric oxide production and expression of NRAMP (natural resistance-associated macrophage protein) genes. This function of IFN-gamma is critical for the human body's resistance to intracellular pathogens. ()

IFN-gamma levels typically increase during infections or immune disorders (eg, autoimmune diseases. This cytokine is part of the Th1 immune response. ()

In addition, interferon gamma is capable of suppressing the growth and stimulating suicide (apoptosis) of many cells, including cancer cells. It is known that IFN-gamma increases the body’s defense against the development of malignant tumors that arise from chemical exposure to harmful substances.

On the other hand, interferon gamma also has a number of negative effects , including suppression of erythropoiesis (formation of red blood cells) and the formation of hematopoietic precursors. In addition, high levels of IFN-γ expression are associated with the development of autoimmune diseases.

The link between increased IFN-γ production and autoimmune diseases is consistent with findings of higher levels of IFN-γ expression in female mice and findings from studies that have shown the female hormone estrogen acts as a facilitator of IFN-γ production .

Scheme of the reaction of the innate part of the immune system to infection with “simple” herpes virus type 2. Recruited inflammatory monocytes lead to the release of the cytokine IL-18, which stimulates NK cells to produce IFN-γ 48 h postinfection. (source)

Interferon gamma interaction with immune cells

Interferon gamma interacts with IFN-gamma-producing immune cells such as T cells, macrophages and dendritic cells in the inflamed or tumor microenvironment.

Macrophages : IFN-gamma stimulates the polarization of macrophages towards their pro-inflammatory M1 phenotype and increases the ability to secrete chemokines.

Dendritic cells : Maturation, up-regulation of MHC I and II through increased IRF1 expression and decreased dendritic cell survival is dependent on IFN-gamma.

T cells : IFN-gamma interacts with T cells, stimulating their transition towards the Th1 subset. Through a positive feedback loop, IFN-gamma stimulates its own production in immune Th1 cells and suppresses the differentiation of Th2 and Th17. IFN-γ is required for the maturation of naïve T cells into effector CD8+ T cells. IFN-gamma is the main cytotoxic molecule secreted by such cells. Immunosuppressive T regulatory cells are suppressed by IFN-gamma.

Scheme of interaction of interferon gamma (IFN-gamma) with immune cells. (source)

References

Lifshits, V.M., Sidelnikova, V.I. Medical laboratory tests. - M.: Triad X, 2007. - 312 p.
Nesterova, I.V. Congenital and acquired interferonopathies: differentiated approaches to interferon-corrective therapy, Federal State Autonomous Educational Institution of Higher Education "Russian Peoples' Friendship University" of the Ministry of Education and Science of the Russian Federation, Moscow, 2021. - V. 16(2). — P. 50-53.
Savenkova, M.S., Karashtina, O.V., Shabat, M.B. and others. Interferon status and choice of interferon inducers in frequently ill children. - Children's infections, 2021. - No. 2. - P. 45-51.

High levels of interferon gamma

Interferon gamma levels generally increase with age. ()

Lipopolysaccharides (LPS, bacterial toxins that cause inflammation and health problems) are one of the most significant triggers for the production of interferon gamma. LPS levels can be elevated by bacterial infections, leaky gut syndrome, or other diseases. ()

Nitric oxide (NO) also increases interferon gamma levels. In addition, nitric oxide is produced by macrophages in response to interferon gamma. ()

Diseases and conditions of the body with high levels of interferon gamma

The diseases or conditions discussed in this section are usually associated with high levels of interferon gamma, but this symptom alone is not enough to make a diagnosis. You should work with your doctor to determine what may be causing your abnormally elevated interferon gamma levels and develop a plan of action to improve your health.

High levels of IFN-gamma can be caused by diseases:

Inflammatory disease of the oral mucosa (eg, recurrent aphthous stomatitis), as shown in a study of 21 people. ()
Patchy hair loss (alopecia areata, an autoimmune disease), as shown in a study of 60 patients. ()
Alcoholism, as seen in a study of 47 chronic alcoholics. ()
Alcohol-induced liver scarring (cirrhosis), as shown in a study of 26 alcoholics. ()
Measles (acute phase, less than 7 days from onset) as shown in a study of 54 patients. ()
Hepatitis B (study of 60 patients) (10)
Tuberculosis, as seen in 2 studies of 10 people with active tuberculosis and 430 patients with latent tuberculosis infection. (, )
Multiple sclerosis (2 studies with a total of 50 people) (, )
Systemic sclerosis (study of 49 patients) ()
Treatment of tuberculosis with isoniazid (study with 26 patients) ()
Melioidosis (infectious bacterial disease, 62 patients). ()

Elevated IFN-gamma levels are usually associated with:

Severe airway inflammation in patients with asthma ()
Severity of psoriasis (, )
The severity of COVID-19 and high mortality ()
Kidney damage in patients with type 2 diabetes mellitus ()
Increased severity of heart disease (coronary heart disease and type 2 diabetes) ()
Progression of the disease amyotrophic lateral sclerosis (ALS) ()
The severity of systemic lupus erythematosus ()
Severity of mixed connective tissue disease ()
The severity of celiac disease upon intake of gluten ()
Stage of malignancy, tumor size and recurrence of liver cancer ()

Interferon gamma mechanisms mediated cancer development. Tumor metastasis can be facilitated by IFN-γ, which induces the expression of ICAM1 and CD13, EMT or CXCR4 and the production of MUC4. (source)

conclusions

To prevent COVID-19, nasal forms of type 1 and type 2 interferons are used. They protect the part of the body that is most vulnerable to coronavirus - the nasal mucosa. The use of nasal medications is recommended for all groups of the population, but especially for people at risk:

doctors of covid departments;
families of the sick;
international tourists;
people with immunodeficiency and concomitant diseases;
elderly;
pregnant women and newborns.

Nasal and systemic preparations of type 1 and 2 interferons are used to treat COVID-19 It is important to start treatment within the first 5 days of the onset of symptoms. Then the disease will pass easier and faster. Late initiation of treatment aggravates coronavirus infection and delays recovery.

IFNs are highly active molecules, therefore treatment with systemic drugs is carried out only by qualified specialists.

What reduces interferon gamma levels

The most important step in reversing elevated interferon gamma levels is to get medical help to identify and treat any underlying conditions that are causing the increase.

You may also want to try some complementary approaches if your doctor thinks they may be helpful for you.

A lifestyle change that will help you not only lower your IFN-gamma levels but also improve your overall health is to exercise more . Endurance training (not moderate exercise) helped reduce IFN-gamma levels in a clinical study of 30 healthy but sedentary men. ()

As mentioned earlier, IFN-gamma levels are elevated in alcoholics. Reducing your alcohol intake can not only reduce your levels of this interferon, but also protect you from the well-known harmful effects of alcohol. ()

A diet high in omega-3 fatty acids may also help reduce IFN-gamma levels, based on preliminary data in mice. Some foods high in omega-3s include fatty fish, shellfish, and fortified dairy products. ()

Some medications, dietary supplements, and substances that have reduced IFN-gamma levels in studies include:

Fish fat ()
Curcumin ()
Olive leaf extract (, )
Andrographis (34, )
Boswellia ()
Lithium()
Theanine ()
Glucosamine ()
Ginkgo biloba ()
Ginseng ()
Theaflavins ()
Nettle leaf ()
EGCG (green tea) ()
Aloe ()
Resveratrol ()
Simvastatin ()
Pterostilbene()
Zinc()
Silymarin (milk thistle) ()
Genistein ()
Acetylcysteine NAC ()
Ibuprofen ()
Sulfasalazine ()
Methotrexate ()
Ozone ()
Oxygen()
Rutin()
Vitamin D ()
Dihydroquercetin (taxifolin) ()
Aspirin ()
Dimethyl fumarate ()

Talk to your doctor before taking any of these substances, and never use them as a substitute for standard treatments for your condition.

Sources

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
Diverse functional autoantibodies in patients with COVID-19
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs
Nasopharyngeal Type-I Interferon for Immediately Available Prophylaxis Against Emerging Respiratory Viral Infections
PROTOCOLO DE ACTUACIÓN NACIONALPARA LA COVID-19
Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV
Efficacy of Interferon Gamma in the Prevention of SARS-CoV-2 Infection (COVID-19): Results of a Prospective Controlled Trial
Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019
Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomized, double-blind, placebo-controlled, phase 2 trial
A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19
Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study
The use of interferon alfa-2b in the complex treatment of patients with COVID-19
Interferon gamma in the treatment of patients with moderate COVID-19
Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2
Therapy of patients with COVID-19: results of assessing the effectiveness and safety of the inclusion of the drug Ingavirin® in the recommended standard therapy regimen in real clinical practice

Articles on similar topics:

Low interferon gamma levels

The diseases or conditions listed here are typically associated with low levels of interferon gamma, but this biomarker alone is not sufficient to make a diagnosis.

Possible causes of low interferon gamma values

Endurance training (especially aerobic) as shown in a clinical study of 30 healthy men. ()
Secondary exposure to cigarette smoke (study of 40 children) ()
Candida albicans – oral cavity infection (study of 26 people) ()
Physical trauma (study, 38 trauma patients) ()
Heart surgery (study of 20 people) ()
Epstein-Barr virus infection (, )
Hepatitis C ()
Treatment with corticosteroids (study of 131 patients with leprosy) ()
Helicobacter pylori infection ()

Helicobacter pylori reduces cholesterol levels in infected gastric epithelial cells and thereby blocks interferon gamma signaling, allowing the bacteria to escape the inflammatory immune response. (source)

What types of interferon are effective against coronavirus infection?

Three types of human interferon are known, differing in the nuances of antiviral activity “Current level of knowledge about human IFN”. All three types have shown to be effective against COVID-19.

Type 1 interferons: alpha (α), beta (β)

Activate the antiviral state of cells.
They trigger the production of proteins that fight the virus at all stages of its life cycle “The role of IFN in the pathogenesis of infectious diseases.”

The most studied member of this family is interferon alpha. It is widely used in different countries of the world against coronavirus infection “Interferon-alpha 2b for the prevention and treatment of COVID-19.”

Interferon beta is also used to treat COVID-19, but has not yet been included in national recommendations. The preventive effectiveness of IFN-beta is still being debated by the scientific community.

Other interferons of this type have been little studied, and there are no approved drugs yet.

Interferon type 3: lambda (λ)

The functions of IFN-3 are similar to IFN-1, their difference is in the scope of action “Types I and III interferons for the fight against COVID-19.” IFN-3 is produced in epithelial cells, such as those of the respiratory tract, and IFN-1 is produced by almost all cells of the body, with the exception of red blood cells and neurons. The study of type 3 interferon is at the stage of clinical trials “The role of IFN-3 in the control of SARS-CoV-2 in intestinal epithelial cells”; there are no approved drugs yet.

Interferon type 2: gamma (γ)

Attracts phagocyte cells to the site of infection to destroy viruses and infected cells.
Increases the activity and survival of phagocyte cells.
Stimulates the acquired immune system to produce highly effective antiviral defense molecules “Immunological memory to the SARS-CoV-2 coronavirus: five components of the immune response.”

The preventive effectiveness of type 2 interferon against coronavirus infection has been confirmed by clinical studies.

In Cuba, type 2 interferon is used in conjunction with IFN-1 to treat COVID-19.

What can increase interferon gamma values?

The most important step if you have low interferon gamma levels is to see your doctor to identify and treat any conditions that may be causing low interferon levels.

You can also try additional approaches if your doctor decides they are helpful for you.

Unlike endurance exercise, moderate exercise may, conversely, increase IFN-gamma production (study of 16 healthy men). ()

exposure to sunlight promotes the release of nitric oxide , which in turn increases interferon gamma levels (clinical study of 24 healthy volunteers). ()

Content

The severity of COVID-19 depends on interferon. How does the level of interferon affect the severity of the disease?

What types of interferon are effective against coronavirus infection?

Prevention

Treatment

Early treatment with interferon reduces mortality and accelerates recovery, later it worsens the disease

Use of interferon in risk groups: type 2 diabetes

Antiviral treatments targeting the interferon system

conclusions

Sources

Structure [edit]

The IFNγ monomer consists of a core of six α-helices and an extensive unfolded sequence in the C-terminal region. [10] [11] This is shown in the structural models below. The α-helices in the core of the structure are numbered from 1 to 6.

Rice. 1.

Linear and cartoon representation of the IFNγ monomer. [eleven]

A biologically active dimer is formed by antiparallel blocking of two monomers, as shown below. In the cartoon model, one monomer is shown in red and the other in blue.

Rice. 2.

Linear and cartoon representation of an IFNγ dimer. [eleven]

Links[edit]

Gray PW, Goeddel DV (August 1982). "Structure of the human immune interferon gene." Nature
.
298
(5877):859–63. Bibcode: 1982Natur.298..859G. DOI: 10.1038/298859a0. PMID 6180322. S2CID 4275528.
Wheelock EF (July 1965). "Interferon-like inhibitor virus induced in human leukocytes by phytohemagglutinin." The science
.
149
(3681):310–1. Bibcode: 1965Sci…149..310W. DOI: 10.1126/science.149.3681.310. PMID 17838106. S2CID 1366348.
Green JA, Cooperband SR, Kibrick S (June 1969). "Immunospecific induction of interferon production in human blood lymphocyte cultures." The science
.
164
(3886):1415–7. Bibcode: 1969Sci...164.1415G. DOI: 10.1126/science.164.3886.1415. PMID 5783715. S2CID 32651832.
Milstone LM, Waxman BH (November 1970). "Release of viral inhibitor from antigen-stimulated tuberculin-sensitized peritoneal cells." Journal of Immunology
.
105
(5):1068–71. PMID 4321289.
↑
Naylor SL, Sakaguchi AY, Shows TB, Law ML, Goeddel DV, Gray PW (March 1983).
"The human immune interferon gene is located on chromosome 12". Journal of Experimental Medicine
.
157
(3):1020–7. DOI: 10.1084/jem.157.3.1020. PMC 2186972. PMID 6403645.
"Entrez Jean: IFNGR2".
"Entrez Jean: INFG".
Schoenborn JR, Wilson CB (2007). "Regulation of interferon-γ during innate and adaptive immune responses". Regulation of interferon gamma during innate and adaptive immune responses
.
Advances in immunology
.
96
. pp. 41–101. DOI: 10.1016/S0065-2776(07)96002-2. ISBN 978-0-12-373709-0. PMID 17981204.
↑
Artis D, Spits H (January 2015).
"Biology of innate lymphoid cells". Nature
.
517
(7534):293–301. Bibcode: 2015Natur.517..293A. DOI: 10.1038/nature14189. PMID 25592534. S2CID 4386692.
Ealick SE, Cook WJ, Vijay Kumar S, M Carson, Nagabhushan TL, Trotta PP, Bugg CE (May 1991). "Three-dimensional structure of recombinant human interferon gamma". The science
.
252
(5006):698–702. Bibcode: 1991Sci…252..698E. DOI: 10.1126/science.1902591. PMID 1902591.
^ abcde PDB: 1FG9; Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, et al (September 2000). "Observation of an unexpected third receptor molecule in the crystal structure of the human interferon-gamma receptor complex". Structure
.
8
(9): 927–36. DOI: 10.1016/S0969-2126(00)00184-2. PMID 10986460.
^ B Sadir R, E Forest, Lortat-Jacob H (May 1998). "Interferon-gamma heparan sulfate binding sequence increased the rate of interferon-gamma interferon-gamma receptor complex formation". Journal of Biological Chemistry
.
273
(18):10919–25. DOI: 10.1074/jbc.273.18.10919. PMID 9556569.
Vanhaverbeke S, Simorre DP, Sadir R, Hansa R, Lortat-Jacob N (November 2004). "NMR characterization of the interaction between the C-terminal domain of interferon gamma and heparin-derived oligosaccharides". Biochemical Journal
.
384
(Pt 1):93–9. DOI: 10.1042/BJ20040757. PMC 1134092. PMID 15270718.
^ ab Lortat-Jacob H, Grimaud JA (March 1991). "Interferon-gamma binds to heparan sulfate via a cluster of amino acids located at the C-terminal part of the molecule". FEBS Letters
.
280
(1):152–4. DOI: 10.1016/0014-5793(91)80225-R. PMID 1901275. S2CID 45942972.
Schroder K, Duke PJ, Rawazite T, Hume D. (February 2004). "Interferon gamma: a review of signals, mechanisms and functions". Journal of Leukocyte Biology
.
75
(2): 163–89. DOI: 10.1189/jlb.0603252. PMID 14525967. S2CID 15862242.
Hoyer FF, Naxerova K, Schloss MJ, Hulsmans M, Nair AV, Dutta P, et al. (November 2021). "Macrophage tissue responses to distant injury influence the outcome of subsequent local immune challenge". Immunity
.
51
(5):899–914.e7. DOI: 10.1016/j.immuni.2019.10.010. PMC 6892583. PMID 31732166.
Yao Y, Jeanathan M, Haddadi S, Barra NG, Vaseghi-Shanjani M, Damjanovic D, et al (November 2021). "Induction of autonomous alveolar memory macrophages requires T cell assistance and is critical for trained immunity". Cell
.
175
(6):1634–1650.e17. DOI: 10.1016/j.cell.2018.09.042. PMID 30433869.
Lakhiram, Rishi Vishal; Zhou, Rui; Verma, Asha Devi; Xia, Bing (2012). "CD4+ T cells: differentiation and function". Journal of Immunological Research
.
2012
. DOI: 10.1155/2012/925135.
Ashkar AA, Di Santo JP, Croy BA (July 2000). "Interferon gamma promotes initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal mouse pregnancy". Journal of Experimental Medicine
.
192
(2):259–70. DOI: 10.1084/jem.192.2.259. PMC 2193246. PMID 10899912.
^ab Razaghi A, Owens L, Heymann K (December 2021). "Review of recombinant human interferon gamma as an immunotherapeutic: influence of production platforms and glycosylation." Journal of Biotechnology
.
240
: 48–60. DOI: 10.1016/j.jbiotec.2016.10.022. PMID 27794496.
Razaghi A, E Tan, Lua LH, Owens L, Karthikeyan OP, Hyman K (January 2017). "Is Pichia pastor a viable platform for the industrial production of recombinant human interferon gamma?" . Biological drugs
.
45
: 52–60. DOI: 10.1016/j.biologicals.2016.09.015. PMID 27810255.
Jump up
↑ Todd PA, Goa KL (January 1992).
“Interferon gamma-1b. A review of its pharmacology and therapeutic potential in chronic granulomatous disease." Drugs
.
43
(1): 111–22. DOI: 10.2165/00003495-199243010-00008. PMID 1372855. S2CID 46986837.
Key LL, Reese WL, Rodriguiz RM, Hatcher HC (July 1992). "Recombinant human interferon gamma therapy for osteopetrosis." Journal of Pediatrics
.
121
(1):119–24. DOI: 10.1016/s0022-3476(05)82557-0. PMID 1320672.
↑
Silverman E (September 2013).
“Marketing of drugs. The line between scientific uncertainty and snake oil promotion." BMJ
.
347
: f5687. DOI: 10.1136/bmj.f5687. PMID 24055923. S2CID 27716008.
"Statement by the Spokesperson Regarding Executive Branch Clemency Grants". whitehouse.gov
. 20 January 2021 - via The National Archives.
Sayer L, Greeley N, Foerster D, Strawser S, Gelbard S, Dong Y, et al (July 2015). "An open-label pilot study of interferon gamma-1b in Friedreich's ataxia." Acta Neurologica Scandinavica
.
132
(1):7–15. DOI: 10.1111/ane.12337. PMID 25335475. S2CID 207014054.
Akhavan A, D Rudikoff (June 2008). "Atopic dermatitis: systemic immunosuppressive therapy." Seminars on skin medicine and surgery
.
27
(2): 151–5. DOI: 10.1016/j.sder.2008.04.004. PMID 18620137.
Schneider LC, Baz Z, Zarcone C, Zurakowski D (March 1998). "Long-term therapy of atopic dermatitis with recombinant interferon gamma (rIFN-gamma)." Annals of Allergy, Asthma and Immunology
.
80
(3): 263–8. DOI: 10.1016/S1081-1206(10)62968-7. PMID 9532976.
Hanifin JM, Schneider LC, Leung DY, Ellis CN, Jaffe HS, Izu AE, et al (February 1993). "Recombinant interferon gamma therapy for atopic dermatitis." Journal of the American Academy of Dermatology
.
28
(2 Pt 1): 189–97. DOI: 10.1016/0190-9622 (93) 70026-р. PMID 8432915.
Abiko K., Matsumura N., Hamanishi J., Horikawa N., Murakami R., Yamaguchi K., et al. (April 2015). "IFN-γ from lymphocytes induces PD-L1 expression and promotes ovarian cancer progression". British Journal of Cancer
.
112
(9):1501–9. DOI: 10.1038/bjc.2015.101. PMC 4453666. PMID 25867264.
Razaghi A, Villacrés S, Jung W, Mashkour N, Butler M, Owens L, Heimann K (October 2021). "Enhanced therapeutic efficacy of expressed recombinant mammalian interferon gamma against ovarian cancer cells". Experimental Cell Studies
.
359
(1):20–29. DOI: 10.1016/j.yexcr.2017.08.014. PMID 28803068. S2CID 12800448.
↑
Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, et al. (September 2000).
"Observation of an unexpected third receptor molecule in the crystal structure of the human interferon-gamma receptor complex". Structure
.
8
(9): 927–36. DOI: 10.1016/S0969-2126(00)00184-2. PMID 10986460.
↑
Kotenko S.V., Izotova L.S., Pollak B.P., Mariano T.M., Donnelly R.J., Muthukumaran G. et al. (September 1995).
"Interactions between components of the interferon gamma receptor complex". Journal of Biological Chemistry
.
270
(36):20915–21. DOI: 10.1074/jbc.270.36.20915. PMID 7673114.
Leon Rodriguez DA, Carmona FD, Echeverría LE, González CI, Martin J (March 2016). "IL18 gene variants influence susceptibility to Chagas disease". PLOS "Neglected Tropical Diseases"
.
10
(3): e0004583. DOI: 10.1371/journal.pntd.0004583. PMC 4814063. PMID 27027876.
Trznadel-Grodzka E, Błaszkowski M, Rotsztejn N (November 2012). “Research on seborrheic dermatitis. Part I. The role of individual cytokines in the pathogenesis of seborrheic dermatitis". Postepy Higieny I Medycyny Doswiadczalnej
.
66
:843–7. DOI: 10.5604/17322693.1019642. PMID 23175340.
Ben-Asouli Y, Banai Y, Pel-Ili Y, Shir A, Kaempfer R (January 2002). “Human interferon gamma mRNA self-regulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR.” Cell
.
108
(2):221–32. DOI: 10.1016/S0092-8674(02)00616-5. PMID 11832212. S2CID 14722737.
Asirvatham AJ, Gregorie CJ, Hu Z, Magner WJ, Tomasi TB (April 2008). "MiRNA Targets in Immune Genes and Dicer/Argonaute and ARE Hardware Components". Molecular Immunology
.
45
(7): 1995–2006. DOI: 10.1016/j.molimm.2007.10.035. PMC 2678893. PMID 18061676.
Chang CH, Curtis JD, Maggi LB, Faubert B, Villarino AV, O'Sullivan D, et al. (June 2013). "Posttranscriptional control of T cell effector function by aerobic glycolysis". Cell
.
153
(6):1239–51. DOI: 10.1016/j.cell.2013.05.016. PMC 3804311. PMID 23746840.

Production[edit]

Recombinant human interferon gamma, as an expensive biopharmaceutical, has been expressed in various expression systems, including prokaryotic, protozoan, fungal (yeast), plant, insect and mammalian cells. Human interferon gamma is commonly expressed in Escherichia coli

, marketed as ACTIMMUNE®, however, the resulting prokaryotic expression system product is not glycosylated with a short half-life in the bloodstream after injection;
The purification process of the bacterial expression system is also very expensive. Other expression systems, such as Pichia pastoris
, have not shown satisfactory results in terms of yield. [20] [21]