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Interferons
See also Individual agents
General information
The interferons, first described in 1957, include at least five natural human glycoproteins (alfa, beta, gamma, omega, and tau). Only the first three types are currently used, and they differ both structurally and antigenically. Interferon alfa is produced by macrophages, B cells, and null lymphocytes, interferon beta by fibroblasts, epithelial cells, and macrophages, and interferon gamma from T lymphocytes and macrophages after antigenic or mitogenic stimulation. The interferons share 30–40% of sequence homology and have antiviral and antiproliferative actions. Interferon gamma, produced by activated T cells and natural killer cells, is recognized by a different receptor and acts primarily as an immunoregulatory cytokine.
Uses
The uses of interferons are listed in Table 1 .
Table 1
Interferons and their indications
| Generic name and trade name | Indications | |
|---|---|---|
| Interferon alfa | Human natural leukocyte interferon alfa (IFNalfa-n3; Alferon) Lymphoblastoid interferon alfa (IFN alfa-n1; Welferon) Recombinant interferon alfa-2a (rIFN alfa-2a; Roferon) Recombinant interferon alfa-2b (rIFN alfa-2b; Intron A) Recombinant interferon alfa-2c (rIFN alfa-2c; Berofor) |
Malignant diseases: hairy cell leukemia, chronic myelogenous leukemia, cutaneous T cell lymphoma, follicular lymphoma, multiple myeloma, Kaposi's sarcoma, diffuse melanoma, renal cell carcinoma, carcinoid tumors Viral diseases: condylomata acuminata, chronic active hepatitis B and C |
| Interferon beta | Natural fibroblast (Fiblaferon) Recombinant interferon beta (rIFN beta; Avonex) Recombinant interferon beta-1b (rIFN beta-1b; Betaseron) |
Multiple sclerosis |
| Interferon gamma | Recombinant interferon gamma-1 b (rIFN gamma-1 b; Actimmune) | Chronic granulomatous disease |
Two authoritative reviews have outlined the therapeutic potential of interferons [ , ]. A wide range of viral diseases or cancers are other candidates for interferon therapy [ ].
Mechanisms of action
On binding to surface receptors, interferon alfa results in activation of cytoplasmic enzymes affecting messenger RNA translation and protein synthesis [ ]. The antiviral state takes hours to develop but can persist for days. Besides broad antiviral activity, interferons are of major importance in regulating immunological functions.
General adverse effects and adverse reactions
Adverse reactions to interferons are multifarious and the natural products seem to be less toxic than the pure synthetic compounds. Influenza-like symptoms with fever, chills, fatigue, myalgia, arthralgia, nausea, and lethargy, starting within 1 week after the start of treatment and lasting 1–7 days, seem to be very common [ , ]. Adverse reactions also include neurotoxicity (paresthesia, polyneuropathy), hepatic toxicity, renal toxicity, and an increase in eyelash growth [ ]. Neutralizing antibodies can lead to resistance in patients with hairy cell leukemia and chronic myeloid leukemia [ , ]. The route of administration influences the provocation of an antibody response, and recombinant interferon beta is more likely to be immunogenic when given subcutaneously or intramuscularly than when given intravenously [ ]. Raynaud’s phenomenon has been described after treatment with interferon alfa [ ], and exacerbation of multiple sclerosis has been observed after treatment with interferon gamma.
The most common adverse effects and reactions reported in two large multicenter studies were fever (60%), leukopenia (43%), increased serum aspartate aminotransferase activity (30%), anorexia (30%), thrombocytopenia (25%), fatigue (21%), nausea, and vomiting (17%) [ , ]. Compared with subcutaneous administration, intravenous interferon alfa is associated with similar adverse effects of greater severity and frequency [ , ].
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