Human Interferon Alpha 2b

[Chanelle Glugla]

Thereconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

Interferon-alpha (IFN-alpha), also known as leukocyte interferon, represents a group of related but distinct proteins that share over 95% amino acid sequence homology. They are members of the type I interferon family which share a common cell surface receptor composed of two subunits, a 100 kDa ligand-binding subunit (IFN-alpha R2) and a 125 kDa ligand binding and signal transduction subunit (IFN-alpha R1) that is involved both in ligand binding and signal transduction. IFN-alpha has both anti-viral and immunomodulatory activities on target cells.

R&D Systems personnel manually curate a database that contains references using R&D Systems products. The data collected includes not only links to publications in PubMed, but also provides information about sample types, species, and experimental conditions.

Interferons (IFNs, /ˌɪntərˈfɪərɒn/ IN-tər-FEER-on[1]) are a group of signaling proteins[2] made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens.[3] Interferons are named for their ability to "interfere" with viral replication[3] by protecting cells from virus infections. However, virus-encoded genetic elements have the ability to antagonize the IFN response, contributing to viral pathogenesis and viral diseases.[4] IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages, and they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (MHC) antigens. Certain symptoms of infections, such as fever, muscle pain and "flu-like symptoms", are also caused by the production of IFNs and other cytokines.

More than twenty distinct IFN genes and proteins have been identified in animals, including humans. They are typically divided among three classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes are important for fighting viral infections and for the regulation of the immune system.

In general, type I and II interferons are responsible for regulating and activating the immune response.[3] Expression of type I and III IFNs can be induced in virtually all cell types upon recognition of viral components, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II interferon is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as T cells and NK cells.[citation needed]

Another function of interferons is to up-regulate major histocompatibility complex molecules, MHC I and MHC II, and increase immunoproteasome activity. All interferons significantly enhance the presentation of MHC I dependent antigens. Interferon gamma (IFN-gamma) also significantly stimulates the MHC II-dependent presentation of antigens. Higher MHC I expression increases presentation of viral and abnormal peptides from cancer cells to cytotoxic T cells, while the immunoproteasome processes these peptides for loading onto the MHC I molecule, thereby increasing the recognition and killing of infected or malignant cells. Higher MHC II expression increases presentation of these peptides to helper T cells; these cells release cytokines (such as more interferons and interleukins, among others) that signal to and co-ordinate the activity of other immune cells.[17][18][19]

Interferons can also suppress angiogenesis by down regulation of angiogenic stimuli deriving from tumor cells. They also suppress the proliferation of endothelial cells. Such suppression causes a decrease in tumor angiogenesis, a decrease in its vascularization and subsequent growth inhibition. Interferons, such as interferon gamma, directly activate other immune cells, such as macrophages and natural killer cells.[17][18][19]

By interacting with their specific receptors, IFNs activate signal transducer and activator of transcription (STAT) complexes; STATs are a family of transcription factors that regulate the expression of certain immune system genes. Some STATs are activated by both type I and type II IFNs. However each IFN type can also activate unique STATs.[22]

In addition to the JAK-STAT pathway, IFNs can activate several other signaling cascades. For instance, both type I and type II IFNs activate a member of the CRK family of adaptor proteins called CRKL, a nuclear adaptor for STAT5 that also regulates signaling through the C3G/Rap1 pathway.[22] Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.[22] Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is also regulated by both type I and type II IFNs. PI3K activates P70-S6 Kinase 1, an enzyme that increases protein synthesis and cell proliferation; phosphorylates ribosomal protein s6, which is involved in protein synthesis; and phosphorylates a translational repressor protein called eukaryotic translation-initiation factor 4E-binding protein 1 (EIF4EBP1) in order to deactivate it.[22]

Interferons can disrupt signaling by other stimuli. For example, interferon alpha induces RIG-G, which disrupts the CSN5-containing COP9 signalosome (CSN), a highly conserved multiprotein complex implicated in protein deneddylation, deubiquitination, and phosphorylation.[24] RIG-G has shown the capacity to inhibit NF-κB and STAT3 signaling in lung cancer cells, which demonstrates the potential of type I IFNs.[citation needed]

Coronaviruses evade innate immunity during the first ten days of viral infection.[37] In the early stages of infection, SARS-CoV-2 induces an even lower interferon type I (IFN-I) response than SARS-CoV, which itself is a weak IFN-I inducer in human cells.[37][38] SARS-CoV-2 limits the IFN-III response as well.[39] Reduced numbers of plasmacytoid dendritic cells with age is associated with increased COVID-19 severity, possibly because these cells are substantial interferon producers.[40]

Delayed IFN-I response contributes to the pathogenic inflammation (cytokine storm) seen in later stages of COVID-19 disease.[41] Application of IFN-I prior to (or in the very early stages of) viral infection can be protective,[37] which should be validated in randomized clinical trials.[41]

Interferon beta-1a and interferon beta-1b are used to treat and control multiple sclerosis, an autoimmune disorder. This treatment may help in reducing attacks in relapsing-remitting multiple sclerosis[43] and slowing disease progression and activity in secondary progressive multiple sclerosis.[44]

Interferon therapy is used (in combination with chemotherapy and radiation) as a treatment for some cancers.[45] This treatment can be used in hematological malignancy, such as in leukemia and lymphomas including hairy cell leukemia, chronic myeloid leukemia, nodular lymphoma, and cutaneous T-cell lymphoma.[45] Patients with recurrent melanomas receive recombinant IFN-α2b.[46]

Unconfirmed results suggested that interferon eye drops may be an effective treatment for people who have herpes simplex virus epithelial keratitis, a type of eye infection.[57] There is no clear evidence to suggest that removing the infected tissue (debridement) followed by interferon drops is an effective treatment approach for these types of eye infections.[57] Unconfirmed results suggested that the combination of interferon and an antiviral agent may speed the healing process compared to antiviral therapy alone.[57]

When used in systemic therapy, IFNs are mostly administered by an intramuscular injection. The injection of IFNs in the muscle or under the skin is generally well tolerated. The most frequent adverse effects are flu-like symptoms: increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning, and depression. Erythema, pain, and hardness at the site of injection are also frequently observed. IFN therapy causes immunosuppression, in particular through neutropenia and can result in some infections manifesting in unusual ways.[58]

Several different types of interferons are approved for use in humans. One was first approved for medical use in 1986.[59] For example, in January 2001, the Food and Drug Administration (FDA) approved the use of PEGylated interferon-alpha in the USA; in this formulation, PEGylated interferon-alpha-2b (Pegintron), polyethylene glycol is linked to the interferon molecule to make the interferon last longer in the body. Approval for PEGylated interferon-alpha-2a (Pegasys) followed in October 2002. These PEGylated drugs are injected once weekly, rather than administering two or three times per week, as is necessary for conventional interferon-alpha. When used with the antiviral drug ribavirin, PEGylated interferon is effective in treatment of hepatitis C; at least 75% of people with hepatitis C genotypes 2 or 3 benefit from interferon treatment, although this is effective in less than 50% of people infected with genotype 1 (the more common form of hepatitis C virus in both the U.S. and Western Europe).[60][61][62] Interferon-containing regimens may also include protease inhibitors such as boceprevir and telaprevir.

Interferons were first described in 1957 by Alick Isaacs and Jean Lindenmann at the National Institute for Medical Research in London;[65][66][67] the discovery was a result of their studies of viral interference. Viral interference refers to the inhibition of virus growth caused by previous exposure of cells to an active or a heat-inactivated virus. Isaacs and Lindenmann were working with a system that involved the inhibition of the growth of live influenza virus in chicken embryo chorioallantoic membranes by heat-inactivated influenza virus. Their experiments revealed that this interference was mediated by a protein released by cells in the heat-inactivated influenza virus-treated membranes. They published their results in 1957 naming the antiviral factor they had discovered interferon.[66] The findings of Isaacs and Lindenmann have been widely confirmed and corroborated in the literature.[68]

3a8082e126