Canis ISSN: 2398-2942

Interferon

Contributor(s): Michael Day, Chris Taylor

Introduction

Name

  • First discovered by Isaacs and Lindeman in 1957.
  • Two formulations of type I interferon have been used in companion animal medicine:
    • Recombinant human interferon alpha (several commercial products, eg Roferon", Intron A") has been used as therapy for a range of feline viral diseases.
    • Recombinant feline interferon omega is a licensed veterinary product (Virbagen Omega") :

Class of drug

  • Biological.

Description

Chemical name

  • Interferon (type I);
    • Interferons a, b, t, and w are classified as Type 1.

Molecular formula

  • Recombinant human interferon alpha, recombinant feline interferon omega.
  • Interferon omega is related to interferon alpha.
  • Recently, genes encoding five subtypes of feline type I interferon have been cloned and sequenced.
  • The five subtypes are approximately 95-99% homologous to each other, but the proteins share only 60% homology with human IFN alpha.
  • This may be taken as evidence to suggest that recombinant feline type I interferon is likely to be more efficacious in the cat than using a cross-reactive human recombinant.

Physical properties

  • Prepared in lyophilized form.

Storage requirements

  • Virbagen Omega" is stored at 4°C (+ /- 2°) (not frozen).

Uses

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Indications

Dog

  • Virbagen Omega" is licensed for the treatment of canine parvovirus infection. The claim for the product is to 'reduce mortality and clinical signs of parvovirosis (enteric form) in dogs from one month of age'. The experimental and field studies supporting this claim are in the published veterinary literature and cited below.

Cat

  • Recombinant feline IFN (Virbagen Omega") is licensed for the treatment of feline viral disease. Field studies of cats with calicivirus infection have shown reduction in the severity and duration of clinical signs related to the virus. In one study, two dose protocols were tested (standard dose of 2.5 MU/kg versus high dose of 5 MU/kg) showing that early treatment with the low dose was more efficacious. In another field study, cats with FeLV infection were treated with recombinant feline IFN or placebo. Results suggested that IFN treated cats had clinical improvement and reduced mortality. Recombinant feline IFN omega (Virbagen Omega") has been shown to be beneficial in the adjunct treatment of chronic gingivitis in cats given subgingivally and subcutaneously. Virbagen Omega" has also been used in the adjunctive therapy of FIP at a dose of 1 MU/kg subcutaneously every other day and then weekly until remission is seen. There are anecdotal reports of oral administration of Virbagen Omega" at 50,000 U daily for treatment of FIP.
  • Roferon" has been used experimentally and anecdotally in the treatment of feline viral infections including FeLV, FIV and FIP.
  • Recombinant human IFN alpha or IFN beta given prophylactically or therapeutically to cats experimentally infected with FIP did not reduce mortality. However, a high dose protocol (10 IU/kg daily for 8 days, then alternate days for 2-3 wk) resulted in temporary suppression of clinical signs and reduced serum antibody titers to FIP, with increased survival time (weeks) compared to untreated cats. There are no good studies of the effect of this treatment in spontaneously arising FIP infection, although one protocol using human interferon alpha orally at 30 IU/day for 7 days on alternate weeks for 6-7 weeks is described.
  • In an experimental setting, recombinant human IFN alpha given in combination with the antiviral drug AZT at the time of infection with FeLV-FAIDS resulted in protection form persistent antigenemia and clinical disease. Seven weeks after starting therapy, anti-IFN antibodies were produced which reduced the effectiveness of therapy.
  • Several studies have shown beneficial effects of oral therapy with recombinant human IFN alpha in cats experimentally infected with FeLV. These effects include clinical improvement (eg increased appetite, weight gain, reduced lethargy) and improved blood cell counts, but there is generally no effect on level of viremia. Other studies have failed to reproduce these beneficial effects, and there are no good studies of the effect of treatment on cats with spontaneously arising infection.
  • Recombinant human interferon alpha has been used topically in cats for the treatment of herpes keratitis at a dose of 20-50 IU/ml reconstituted in artificial tears and given twice daily.
  • Clinical projects are underway to look at potential benefits of Virbagen Omega" therapy of chronic gingivostomatitis associated with chronic calicivirus infection in cats.

Administration

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Pharmocokinetics

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Precautions

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Interactions

with other drugs

  • Virbagen Omega" should not be administered with any other biologicals or vaccines. Roferon" has been administered experimentally to cats with FeLV infection concurrently with the antiviral AZT.

with diagnostic tests

  • Virbagen Omega" may result in a slight pancytopenia in dogs that is reversed in one week.

Adverse Reactions

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Further Reading

Publications

Refereed papers

  • de Mari, Maynard L, Sanquer A, Lebreux & Eun H M (2004)Therapeutic effects of recombinant feline interferon-omega onfeline leukemia virus (FeLV)-infected and FeLV/feline immunodeficiency virus (FIV)-coinfected symptomatic cats.J Vet Intern Med18(4), 477-482PubMed.
  • Ishida T, Shibanai A, Tanaka S, Uchida K & Mochizuki M (2004)Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis.J Feline Med Surg6(2), 107-109PubMed.
  • de Mari Ket al(2003)Treatment of canine parvoviral enteritis with interferon omega in a placebo-controlled field trial.Vet Rec152, 105-108PubMed.
  • Mihaljevic S Y (2003)First clinical experiences with omega-interferon in the treatment of chronic gingivitis-stomatitis-oropharyngitis of cats.Praktische Tierarzt.84, 350-361.
  • Riondato Fet al(2003)Effects of interferon alpha therapy on peripheral blood lymphocyte subsets from FIV and FeLV naturally infected cats.Vet Res Comm.27, 429-432PubMed.
  • Martin Vet al(2002)Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled challenge trial.Vet Microbiol.89, 115-127PubMed.
  • McCaw DLet al(2001)Immunomodulation therapy for feline leukaemia virus infection.J Am Anim Hosp Assoc.37, 356-363PubMed.
  • Kolbl Set al(2000)Effects of long term low dose interferon alpha in cats persistently infected with FeLV.Kleintierpraxis45, 497.
  • Cummins J Met al(1999)Oral use of interferon.J Interferon Cytokine Res.19, 853-857PubMedDOI.
  • Minagawaet al(1999)Feline interferon-omega treatment on canine parvovirus infection.Vet Microbiol.69, 51-53PubMed.
  • Kruth S A (1998)Biological response modifiers: interferons, interleukins, recombinant products, liposomal products.Vet Clin North Am Small Anim Pract.28, 269-295PubMed.
  • Ishiwata Ket al(1998)Clinical effects of the recombinant feline interferon-omega on experimental parvovirus infection in beagle dogs.J Vet Med Sci.60, 911-917PubMed.
  • Kociba G Jet al(1995)Effects of orally-administered interferon-alpha on the pathogenesis of feline leukaemia virus-induced erythroid aplasia.Comp Haematol Int5, 79-83.
  • Uchino T (1995)Future prospect of feline interferon in prevention of viral disorders.J Vet Intern Med.48, 663-666.

Other sources of information

  • Day M J (2002)Immunomodulatory Therapy. Chapter 11, In: Maddison J, Page S & Church D (eds)Small Animal Clinical Pharmacology. W B Saunders, 2002, pp.233-249.
  • Maynardet alEfficacy of a recombinant feline omega interferon in the treatment of symptomatic FeLV or FeLV and FIV positive cats. Proceedings 10th ESVIM.
  • http://www.dr-addie.com/treatment.htm#Interferon
  • http://www.virbagenomega.com

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