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ORIGINAL ARTICLE
Year : 1984  |  Volume : 32  |  Issue : 5  |  Page : 429-431

Interferon and ocular virus disease


Department of Ophthalmology, West Virginia University, Morgantown. West Virginia, USA

Correspondence Address:
V K Raju
Department of Ophthalmology, West Virginia University, Morgantown, West Virginia
USA
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Source of Support: None, Conflict of Interest: None


PMID: 6085834

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How to cite this article:
Raju V K. Interferon and ocular virus disease. Indian J Ophthalmol 1984;32:429-31

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Raju V K. Interferon and ocular virus disease. Indian J Ophthalmol [serial online] 1984 [cited 2021 Sep 21];32:429-31. Available from: https://www.ijo.in/text.asp?1984/32/5/429/27531



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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.[1] 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[2] 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."[3]

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.[5]

(b) Adenoviral keratoconjunctivitis: The use of interferon (a) in minimizing symptoms of this disease has been reported recently.[6] 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.[8] Since then, topically applied leucocvte interferon has been tested for the treatment of experimental herpes keratitis.[9] 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.[10] 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.[11],[12]


  Toxicity of interferon Top


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.


  Conclusions Top


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.


  Future Top


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.

 
  References Top

1.
Isaacs A., Lindenmann J., 1957. Proc R Soc. Lond 147: 258.  Back to cited text no. 1
    
2.
M.Ho., 1982. Pharmacological Reviews. Vol 34. No. 1,119.  Back to cited text no. 2
    
3.
Meeting sponsored by the National Institute of Allergy and Infectious Diseases. Nature. 286: 116, 10 July 1980.  Back to cited text no. 3
    
4.
Pollard R.B., 1982. Drugs. 23: 37.  Back to cited text no. 4
    
5.
Jones B.R.. Gulbraith J.E.K. Al-Hussaini M.K: 1962. Lancet 1: 875.  Back to cited text no. 5
    
6.
Negoro Y., Imanishi J., Matsuo A., et al., 1980. JapaneseJ of Ophthalmol. 24: 125.  Back to cited text no. 6
    
7.
Romano A., Revel M., Guareri-Rotman D. et al., 1980. J of Interferon Research. 1: 95.  Back to cited text no. 7
    
8.
Kaufman H.E., 1962. Arch. of Ophthalmol. 67: 346.  Back to cited text no. 8
    
9.
Kaufman H.E., Ellison E.D., Centifanto Y.M..1972. Amer J Ophthalmol. 74: 89.  Back to cited text no. 9
    
10.
Jones B.R., Coster DJ., Falcon M.G., Cantell K., 1976. Lancet. 2: 128.  Back to cited text no. 10
    
11.
How they did it, 1980. Synthesis of interferon. JAMA, 243 (8): 721. .  Back to cited text no. 11
    
12.
Sanitato J.J., Varnell E.D., Kaufman H.E.. Raju V.K Differences in native and recombinant interferon for herpes keratitis in two animal models (in press).  Back to cited text no. 12
    



 
 
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