Classification and production methods
In medical practice, interferon (IFN) preparations are classified according to two main criteria: chemical-biological properties and production technology.
Based on chemical and biological properties, six types are distinguished. The most clinically significant are IFN-α (alpha), IFN-β (beta), and IFN-γ (gamma). There are also IFN-δ (delta), IFN-ω (omega), and IFN-τ (tau).
According to the production method, there are two major groups of dosage forms:
- Natural preparations. These are obtained from a culture of leukocytes isolated from donor blood. To trigger interferon synthesis, the cells are induced with a specific virus. This group includes IFN-α, IFN-β, as well as IFN-α-n1.
- Recombinant preparations. These are the product of modern genetic engineering. Under laboratory conditions, a plasmid containing the human interferon gene is inserted into bacterial strains, after which the bacteria begin to synthesize the desired glycoprotein. Examples of such agents include IFN-α-2a, IFN-α-2b, and IFN-α-1b.
Pharmacokinetics and mechanism of action
The pharmacokinetics of interferons has strict limitations. These drugs are completely inactive when administered orally, as their protein structure is rapidly destroyed in the gastrointestinal tract. Therefore, they are administered exclusively parenterally (subcutaneously, intramuscularly, or intravenously) or applied topically.
The initial stage of the drug's action consists in the interaction of the molecule with specific receptors located on the membrane of target cells. This binding triggers a complex cascade of intracellular reactions, which leads to the induction of the synthesis of various enzymes.
At the cellular level, interferons exert three main effects: antiviral, antitumor, and immunomodulating.
- Antiviral mechanism: interferon activates a specific enzyme that directly inhibits (blocks) the translation of viral RNA. This prevents further replication of the virus inside the cell.
- Effect on the cell cycle: the drugs exercise strict control over cell proliferation (division), regulate their differentiation, and can trigger apoptosis (programmed cell death) of defective structures.
- Immune response: activation of immune effectors—macrophages—occurs, as well as a significant increase in the cytotoxicity of lymphocytes.
Clinical application
Indications for prescription depend on the specific type of interferon and its dosage form.
- IFN-α (alpha) preparations have the broadest spectrum of applications. In infectiology, they are prescribed for viral hepatitis B and C, HIV infection, and papillomavirus infection. In oncology practice, they have proven effective in treating Kaposi's sarcoma, various leukemias, and melanoma.
- IFN-β (beta) preparations have found their niche in neurology. They are used as powerful immunomodulators in the combination therapy of multiple sclerosis.
- IFN-γ (gamma) preparations (e.g., Ingaron) are used to treat severe pathologies, specifically chronic granulomatous disease.
- Local and topical application covers different types of IFN:
- Ophthalmology: treatment of herpetic eye lesions (drops and subconjunctival injections are used).
- Dermatovenereology: therapy of herpes simplex (localized on the skin, mucous membranes, and genitals) and herpes zoster. Special hydrogel-based ointments are used for this purpose.
- Respiratory infections: prevention and treatment of influenza and ARVI using intranasal drops.
Side effects
Despite high efficacy, interferon therapy is characterized by a wide range of side effects. The most frequent adverse event is influenza-like syndrome.
In addition, the drugs can have a negative impact on various organ systems:
- Central nervous system (CNS): patients often complain of dizziness, visual disturbances, insomnia, and tremor. In severe cases, confusion, depression, and paresthesia may occur.
- Gastrointestinal tract (GI): nausea and pronounced loss of appetite are characteristic.
- Hematopoiesis and kidneys: transient leukopenia and proteinuria may be observed in laboratory tests.
- Cardiovascular system: symptoms of heart failure may appear.
- Other reactions: dermatological manifestations (skin rash, itching, alopecia), nosebleeds, and temporary impotence.
Briefly: answers to topical questions
Which specific drugs belong to the group of recombinant interferons?
Recombinant interferons obtained by genetic engineering include:
- Interferon alfa-2a
- Interferon alfa-2b
- Interferon alfa-1b
- Reaferon — recombinant interferon alfa
- Betaferon — recombinant interferon beta
What specific enzymes are synthesized in the cell under the action of interferons?
Under the action of interferons, the synthesis of key effector proteins and specific enzymes ensuring the antiviral effect is triggered in the cell:
- Oligoadenylate 2'-5' (A) synthetase (Oligoadenylate-2'-5'-synthetase) — activates cellular endoribonuclease (RNase L), which cleaves viral RNAs
- Protein kinase R (PKR) (Protein kinase P1) — a serine/threonine kinase that phosphorylates translation initiation factor eIF-2 and cellular enzymes, blocking protein synthesis
- Mx protein (Mx protein) — binds to the viral RNA polymerase, halting its replication
Which exact receptors do interferons bind to on the membrane of target cells?
Interferons bind to specific membrane receptors on the surface of target cells, which are subdivided into families depending on the type of interferon:
- Type I interferon receptor (IFNAR) — consists of two molecular chains: IFNAR1 (or β1) and IFNAR2 (or β2), to which alpha and beta interferons bind simultaneously
- Type III interferon receptor — represented by two molecules: IFNAR1 and IL10R2, containing a chain shared with the interleukin-10 receptor
What changes in blood tests can interferon therapy cause?
Interferon therapy can lead to changes in blood parameters, among which the development of transient leukopenia is noted as a hematological side effect affecting the hematopoietic system.
To memorize the main indications of the three main types, use the mnemonic: Alpha — Attacks viruses and tumors (hepatitis, melanoma), Beta — Blocks autoimmune aggression (multiple sclerosis), Gamma — Granulomatosis.
Class and exam questions
Why are interferons not manufactured as oral tablets?
Interferons have a protein structure (they are glycoproteins), therefore, upon oral administration, they are completely destroyed by gastrointestinal enzymes and lose their pharmacological activity.
What is the difference between natural and recombinant interferons?
Natural preparations are obtained from human donor leukocytes after stimulation with an inducing virus. Recombinant ones are produced by genetic engineering methods, cultivating bacterial strains with an integrated human interferon gene plasmid.
How exactly does interferon halt a viral infection?
It does not destroy the virus directly. The drug binds to cell receptors and induces the synthesis of a specific enzyme that blocks viral RNA translation, making viral replication impossible.
What else to study on this topic
- The process of obtaining natural interferons from a donor leukocyte culture.
- The technology of cultivating bacterial strains to produce recombinant IFNs.
- Mechanisms of cell cycle control, proliferation, and apoptosis initiation.
- Specific enzymes inhibiting viral RNA translation.
- Use of IFN-alpha preparations in oncology (melanoma, Kaposi sarcoma, leukemias).
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