IntronA (Interferon alpha 2b)
An overview of IntronA (Interferon alpha 2b)
IntronA, also known as interferon α-2b (IFNα2b), is a drug used in antiviral and anti-tumor therapeutic treatments [1]. IFNα2b is classified as a cytokine, a secreted protein that stimulates the immune system, and is produced by T-cells in order to hinder viral infections, cancer, bacteria, or other pathogens in humans [1].
FunctionIFNα2b is a naturally secreted protein that is produced by the human body via antigen-presenting cells (APCs) [1]. When introduced to the body for treatment, IFNα2b is injected into the body subcutaneously and binds to the surface of cells [2]. When this occurs, IFNα2b produces many possible outcomes. This includes inhibiting replication of viruses within virus-infected cells, suppressing cell proliferation, enhancing activity of macrophages, stimulating certain types of enzymes, and increasing lymphocytes’ specific cytotoxicity [2]. Specifically in viral infections and malignancy, the interferon targets CD8+ effector T cells and CD4+ immunomodulatory T cells to amplify the body’s immune response [1]. It can also help induce a caspase cascade to activate cell death in virally infected and malignant cells [1]. Overall, INFα2b is crucial for activation and regulation of the protective immune response. Structural highlightsEach IFNα2b monomer consists of five alpha helices and five coiled loops [3]. A zinc molecule is held within each IFNα2b monomer [3]. There are four significant cysteine residues on IFNα2b that create two disulfide bonds [4]. The first disulfide bond is between Cys29 and Cys138 [4]. The second disulfide bond is between Cys1 and Cys98 [4]. IFNα2b is considered a Type I interferon and recognizes interferon alpha receptors 1 and 2 located on the target protein’s surface [4]. Amino acid residues on IFNα2b that participate in binding to IFNAR 1 and 2 are present on one coiled loop and four alpha helices [4]. These residues include: Arg22, Leu26, Phe27, Leu30, Lys31, Arg33, His34, Ser68, Thr79, Lys83, Tyr85, Tyr89, Arg120, Lys121, Gln124, Lys131, Glu132, Arg144, and Glu146 [4]. MechanismThere are several pathways in which IFNα2b has an effect on the target cell [4]. These pathways include the caspase cascade and the JAK-STAT pathway [4] [1]. The caspase cascade results in apoptosis, thereby participating in both anti-viral and anti-cancer mechanisms [1]. Once IFNα2b binds to either IFNAR 1 or 2 receptors, cytochrome c and tumor necrosis alpha factor trigger the caspase cascade, which in turn signals apoptosis [4]. In the binding of IFNα2b to an IFNAR receptor, the protein JAK (a tyrosine kinase) is activated [4]. JAK is phosphorylated and in turn phosphorylates the IFNAR receptors [4]. The IFNAR receptors bind to STAT proteins resulting in a cascade pathway that signals the release of antiviral proteins [4]. DiseaseHepatitis Virus Hepatitis B IFNα2b treats chronic Hepatitis B (HBV) by interfering with viral DNA synthesis and enhancing the cellular immune response [5]. The cytokine enhances T-cell and natural killer cell activity by interacting with the infected cell’s surface [5]. IFNα2b also activates antiviral enzymes to inhibit proliferation of HBV [5]. Hepatitis C Hepatitis C (HCV) can range from acute to chronic conditions and progression occurs in more than half of these cases [6]. HCV attacks the liver tissues causing inflammation and cirrhosis, which can lead to chronic liver disease [6]. IFNα2b is used to treat the acute stage of HVC to prevent progression into the chronic disease [6]. IFNα2b overall reduces the viral amplification and allows T-cells to effectively respond to the infection [7]. Cancer Multiple Myeloma IFNα2b has been shown to prolong patients with multiple myeloma [8]. Multiple myeloma is diagnosed when multiple clones of a specific plasma cell are found or when apparent genetic mutations are affecting the cell’s normal functions [8]. IFNα2b therapy causes tumor stabilization and prolongation of the aggressive stage of multiple myeloma with maintained therapy [8]. Hairy cell Leukemia IFNα2b is a major treatment for patients with hairy cell leukemia [4]. The disease is characterized by B cells in the blood, bone marrow, and spleen [4]. Patients who receive the therapeutic treatment experience partial to complete remission [4]. The treatment is especially effective because there is rarely relapse of the cancer with consistent therapy and mild side effects [4]. The presence of malignant cells decreases, predominantly in the bone marrow, and hematologic levels normalized [9]
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References
- ↑ 1.0 1.1 Asmana Ningrum R. Human interferon alpha-2b: a therapeutic protein for cancer treatment. Scientifica (Cairo). 2014;2014:970315. doi: 10.1155/2014/970315. Epub 2014 Mar, 10. PMID:24741445 doi:https://dx.doi.org/10.1155/2014/970315
