Interferon-gamma
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
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Overview
Interferon-gamma is an immunological agent that is FDA approved for the treatment of serious infections associated with Chronic Granulomatous Disease and delaying time to disease progression in patients with severe, malignant osteopetrosis.. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding Interferon-gamma FDA-Labeled Indications and Dosage (Adult) in the drug label.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Interferon-gamma in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Interferon-gamma in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Interferon-gamma FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Interferon-gamma in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Interferon-gamma in pediatric patients.
Contraindications
There is limited information regarding Interferon-gamma Contraindications in the drug label.
Warnings
There is limited information regarding Interferon-gamma Warnings' in the drug label.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Interferon-gamma Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Interferon-gamma Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Interferon-gamma Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Interferon-gamma in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Interferon-gamma in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Interferon-gamma during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Interferon-gamma in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Interferon-gamma in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Interferon-gamma in geriatric settings.
Gender
There is no FDA guidance on the use of Interferon-gamma with respect to specific gender populations.
Race
There is no FDA guidance on the use of Interferon-gamma with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Interferon-gamma in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Interferon-gamma in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Interferon-gamma in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Interferon-gamma in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Interferon-gamma Administration in the drug label.
Monitoring
There is limited information regarding Interferon-gamma Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Interferon-gamma and IV administrations.
Overdosage
There is limited information regarding Interferon-gamma overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
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Interferon-gamma
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Systematic (IUPAC) name | |
Human interferon gamma-1b | |
Identifiers | |
CAS number | 98059-61-1 |
ATC code | L03 |
PubChem | ? |
DrugBank | |
Chemical data | |
Formula | Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox |
Mol. mass | 17145.6 g/mol |
Pharmacokinetic data | |
Bioavailability | ? |
Metabolism | ? |
Half life | ? |
Excretion | ? |
Therapeutic considerations | |
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Routes | ? |
Mechanism of Action
There is limited information regarding Interferon-gamma Mechanism of Action in the drug label.
Structure
There is limited information regarding Interferon-gamma Structure in the drug label.
Pharmacodynamics
There is limited information regarding Interferon-gamma Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Interferon-gamma Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Interferon-gamma Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Interferon-gamma Clinical Studies in the drug label.
How Supplied
There is limited information regarding Interferon-gamma How Supplied in the drug label.
Storage
There is limited information regarding Interferon-gamma Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Interferon-gamma Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Interferon-gamma interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Interferon-gamma Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Interferon-gamma Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
Interferon, gamma | |||
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Interferon gamma, line representation | |||
Identifiers | |||
Symbols | IFNG ; IFG; IFI | ||
External IDs | Template:OMIM5 Template:MGI HomoloGene: 55526 | ||
RNA expression pattern | |||
More reference expression data | |||
Orthologs | |||
Template:GNF Ortholog box | |||
Species | Human | Mouse | |
Entrez | n/a | n/a | |
Ensembl | n/a | n/a | |
UniProt | n/a | n/a | |
RefSeq (mRNA) | n/a | n/a | |
RefSeq (protein) | n/a | n/a | |
Location (UCSC) | n/a | n/a | |
PubMed search | n/a | n/a |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]
Interferon-gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons.[1] This interferon was originally called macrophage-activating factor.
Structure of IFN-γ
The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region.[2][3] This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6.
The biologically active dimer is formed by anti-parallel inter-locking of the two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue.
The structural models shown above (see protein data bank code 1FG9) are all shortened at their C-termini by 17 amino acids. Full length IFN-γ is 143 amino acids in length, the models are 126 amino acids in length. Affinity for the glycosaminoglycan heparan sulfate resides solely within the deleted sequence of 17 amino acids.[4]
Biological activity
In contrast to interferon-α and interferon-β which can be expressed by all cells, IFN-γ is secreted by Th1 cells, Tc cells, dendritic cells and NK cells. Also known as immune interferon, IFN-γ is the only Type II interferon. It is serologically distinct from Type I interferons and it is acid-labile, while the type I variants are acid-stable.
IFN-γ has antiviral, immunoregulatory, and anti-tumour properties.[5] It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Amongst the effects are:
- Increase antigen presentation of macrophages.
- Activate and increase lysosome activity in macrophages
- Suppress Th2 cell activity.
- Cause normal cells to express class II MHC molecules
- Promotes adhesion and binding required for leukocyte migration
- Promotes NK cell activity
Activation by IFN-γ is achieved by its interaction with a heterodimeric receptor consisting of IFNGR1 & IFNGR2 (interferon gamma receptors). IFN-γ binding to the receptor activates the JAK-STAT pathway. In addition, IFN-γ activates APCs and promotes Th1 differentiation by upregulating the transcription factor T-bet.
IFN-γ is the hallmark cytokine of Th1 cells (Th2 cells produce IL-4). NK cells and CD8+ cytotoxic T cells also produce IFN-γ. IFN-γ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NFκB.
Therapeutic uses
File:Interferon-gamma.png | |
Clinical data | |
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DrugBank | |
E number | {{#property:P628}} |
ECHA InfoCard | {{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value). |
Chemical and physical data | |
Formula | C761H1206N214O225S6 |
Molar mass | 17145.6 g/mol |
Interferons are used to treat infectious diseases and cancer.
Scientists at the University of California at Berkeley have recently discovered that Diindolylmethane (DIM), a naturally occurring compound found in Brassica vegetables, upon oral consumption, is a direct and potent activator of Interferon-Gamma production and sensitivity within the body leading the way for the study of this compound as an anti-viral, anti-bacterial and anti-cancer therapeutic. As this is a dietary compound found in edible vegetables, this has caused a lot of excitement in the immunology field. This compound has also been shown to synergize with Interferon-Gamma in the expression and potentiation of the MHC-I Complex, leading to its study as a possible adjuvant to Interferon-gamma therapeutic models.
References
- ↑ Gray, P. W. and Goeddel, D. V. (1982). "Structure of the human immune interferon gene". Nature. 298: 859–863. doi:10.1038/298859a0.
- ↑ Ealick, S. E., Cook, W. J.; et al. (1991). "Three-dimensional structure of recombinant human interferon-gamma". Science. 252: 698–702. doi:10.1126/science.1902591.
- ↑ Thiel, D. J.; et al. (2000). "Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complex". Structure. 8 (9): 927–936. doi:10.1016/S0969-2126(00)00184-2.
- ↑ Vanhaverbeke, C. Simorre, J-P.; et al. (2004). "NMR characterization of the interaction between the C-terminal domain of interferon-γ and heparin-derived oligosaccharides". 384: 93–99. PMID 15270718.
- ↑ Schroder; et al. (2004). "Interferon-γ an overview of signals, mechanisms and functions". Journal of Leukocyte Biology. 75: 163–189. doi:10.1189/jlb.0603252.
Further reading
- Hall, Steven S. (1997) A Commotion in the Blood. New York, New York: Henry Holt and Company. ISBN 0-8050-5841-9
- Information on Interferon and how it relates to hepatitis c
- Ikeda H, Old LJ, Schreiber RD (2002). "The roles of IFN gamma in protection against tumor development and cancer immunoediting". Cytokine Growth Factor Rev. 13 (2): 95–109. PMID 11900986.
- Chesler DA, Reiss CS (2003). "The role of IFN-gamma in immune responses to viral infections of the central nervous system". Cytokine Growth Factor Rev. 13 (6): 441–54. PMID 12401479.
- Dessein A, Kouriba B, Eboumbou C; et al. (2005). "Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis". Immunol. Rev. 201: 180–90. doi:10.1111/j.0105-2896.2004.00195.x. PMID 15361241.
- Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. PMID 15638726.
- Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini reviews in medicinal chemistry. 5 (12): 1093–101. PMID 16375755.
- Chiba H, Kojima T, Osanai M, Sawada N (2006). "The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease". Sci. STKE. 2006 (316): pe1. doi:10.1126/stke.3162006pe1. PMID 16391178.
- Tellides G, Pober JS (2007). "Interferon-gamma axis in graft arteriosclerosis". Circ. Res. 100 (5): 622–32. doi:10.1161/01.RES.0000258861.72279.29. PMID 17363708.
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