Year : 1984 | Volume
: 32 | Issue : 5 | Page : 429--431
Interferon and ocular virus disease
Department of Ophthalmology, West Virginia University, Morgantown. West Virginia, USA
V K Raju
Department of Ophthalmology, West Virginia University, Morgantown, West Virginia
|How to cite this article:|
Raju V K. Interferon and ocular virus disease.Indian J Ophthalmol 1984;32:429-431
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Raju V K. Interferon and ocular virus disease. Indian J Ophthalmol [serial online] 1984 [cited 2022 Jul 5 ];32:429-431
Available from: https://www.ijo.in/text.asp?1984/32/5/429/27531
Interferons are a family of secretory glycoproteins produced by most eukaryotic cells in response to a variety of viral and nonviral stimuli (inducers). Since the accidental discovery of interferon in 1957 by Isaacs and Lindenmann "as an antiviral substance produced by cells in response to virus infection," interferon has been shown to affect other vital cellular and bodily functions not directly connected with viral replication. For example, interferon may: (1) inhibit the division of a variety of cells, (2) affect the immune response, (3) affect expression of cell membrane antigens and receptors and (4) influence the body's response to ionizing radiation.
More than 25 years of research has produced great advances in the understanding of interferon This brief review presents recent advances in human interferon system and potential clinical applications relevant to ocular virus disease.
Interferon nomenclature: Recently an international group of scientists standardized the nomenclature and classified the interferons accepting as a definition that "To qualify as an interferon a factor must be a protein which exerts virus nonspecific, antiviral activity at least in homologous cells through cellular metabolic processes involving synthesis of both RNA and protein."
Interferons are classified into types on the basis of antigenic specificities, type designations to be alpha (a), beta (b), and gama (y), corresponding to previous designations of Leucocyte (Le) fibroblast (F) and type II (immune) interferons respectively [Table 1].
Inducers and Interferon Induction: Viruses were the first inducers of interferon discovered. Human leucocyte interferon (alpha) is produced by buffy coat cells following induction by Sendai virus. The basis of interferon induction by viruses may be double stranded RNA. Some viruses contain double stranded RNA while others may make RNA during the course of viral replication. However, there are many other types of inducers such as polysaccharides and micro-organisms that cannot be explained on the basis of nucleic acid which may act on macrophages to induce interferon by different pathways4
Since interferon is species specific, and homologous interferon, is difficult and expensive to obtain, many studies have been done with interferon inducers. A synthetic double stranded RNA. Polyinosinic-polycytidylic acid (Poly I:C) has been the most widely used because of its relative low toxicity and favourable inducing properties. But in spite of initial optimism about using Poly I:C in the treatment of herpes simplex keratitis, it has not proved to be more effective than other antiviral agents. Another compound, Tilorone hydrochloride (interferon inducer) was associated with significant local toxicity and thus not indicated for topical therapy.
The present outlook for usage of interferon inducers to treat herpetic disease of the cornea is unfavourable.
Mechanism of Action: It was clear in early studies on the antiviral action of interferon that it did not inactivate the virus directly, rather rendered cells resistant to virus. Interferon acts on the cell, not the virus, by inhibiting the transcriptive or translational ability of viral nucleic acid enabling each species to produce its own species-specific interferon. As a general rule, interferons are most active antivirally when incubated with cells of the species from which they are induced, although cross-species activity does occur.
Local administration of interferon
(a) Vaccinial keratitis: Jones et al reported that the severity of vaccinial keratitis was decreased in monkeys by topical interferon use although deeper stromal disease was not affected.
(b) Adenoviral keratoconjunctivitis: The use of interferon (a) in minimizing symptoms of this disease has been reported recently. In a double blind controlled study, interferon (b) decreased the length of adenoviral keratoconjunctivitis from more than 10 days to 6-7 days. Additionally, the development of keratitis was markedly decreased in the interferon group when compared with the group receiving placebo.
(c) Herpes simplex keratitis: Interferon as a potential ocular antiviral agent was proposed as early as 1962. Since then, topically applied leucocvte interferon has been tested for the treatment of experimental herpes keratitis. Various studies have shown that interferon exerts a prophylactic effect against both primary and recurrent ocular herpetic infection in rabbits and owl monkeys but interferon as a therapeutic agent in herpetic keratitis is somewhat disappointing. In 1962, Kaufman proposed its use as a topical antiviral agent. Since then,, various investigators in clinical situations have used interferon with some success in combination with thermocautery or debridement. However, both expense and complexity of preparation prevented interferon from becoming a practical agent for the treatment or prevention of herpetic keratitis.
Recent advances in recombinant DNA technology have resulted in the commercial synthesis of recombinant leucocyte interferon which is now relatively inexpensive and available in large enough quantities to support widespread experimental usage.,
TOXICITY OF INTERFERON
Toxic reactions reported depend on the route of administration and the purity of preparation being utilized. However, since its discovery, interferon has been purified over 50,000 times. Topical administration of human IFN-a has not been associated with significant toxic reactions although systemic administration of interferon may lead to granulocytopenia, thrombocytopenia etc.
Experimental and clinical trials with interferon in herpetic keratitis and other viral infections of the eye, though severely limited by the scarcity of the material available, are somewhat encouraging. Although systemic administration of interferon is not without. side effects, topically administered interferon to the eye does not seem to produce any toxic reactions.
The successful isolation of genes for both IFN (alpha) and IFN (beta) and their implantation into bacteria which then produces large amounts of these materials is a major breakthrough of this decade as it eliminates cumbersome methods of producing interferon. With the availability of large amounts of more purified material, it is likely that some modification of the interferon system will be found useful in the prevention of recurrent herpetic keratitis.
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