Web Chapter 40 Previous studies have shown that inflammatory mediators such as granulocyte-monocyte colony-stimulating factor (GM-CSF) are produced by keratinocytes in atopic dermatitis lesions, and GM-CSF has been shown to be significantly increased in human with atopy. An in vitro study demonstrated that rCaIFN-γ suppressed messenger RNA transcription of GM-CSF in cultured canine keratinocytes (Shibata et al, 2010). There are a number of anecdotal reports of the treatment of animal skin diseases using recombinant human IFN-α2b (rHuIFNα2b) and IFN-α2a (rHuIFNα2a). In one published report, oral rHuIFNα2b was used for the management of idiopathic recurrent canine pyoderma at a dosage of 1000 U/ml/day and was found to provide transient benefits compared with placebo (Thompson et al, 2004). rHuIFNα was administered at a dosage of 1 million U/kg three times a week SC for 2 weeks to treat canine papillomavirus–associated hamartoma and squamous cell carcinoma, but the efficacy of the therapy in these conditions is uncertain (Callan et al, 2005). rCaIFN-γ is produced by silkworms via the transfer of canine full-length IFN-γ genes. It was launched on the Japanese market for the treatment of canine atopic dermatitis in 2005. Six subcutaneous injections of rCaIFN-γ given in two consecutive weeks modified TH1 and TH2 cytokine messenger RNA profiles for IL-4 and IFN-γ toward TH1 cytokine predominance. Treatment yielded improvement of clinical signs in 10 atopic dogs (Iwasaki et al, 2005). It also decreased total immunoglobulin E in sera, although levels of allergen-specific immunoglobulin E were not determined. Recently a randomized clinical trial of rCaIFN-γ was performed in 63 atopic dogs in which rCaIFN-γ was administered at a dosage of 10,000 U/kg three times a week SC for 4 weeks, followed by once-a-week administration for 4 weeks. Seventy-two percent of the dogs treated with rCaIFN-γ showed improvement (defined as >50% reduction of pruritus), compared with only 20% in the control group given antihistamine spray (Iwasaki and Hasegawa, 2006). Based on this study the manufacturer recommended a dosage of rCaIFN-γ of 10,000 U/kg three times a week SC. The dosage of rCaIFN-γ required for the treatment of canine atopic dermatitis was investigated further in 2010. Yasukawa and colleagues evaluated the efficacy of low-dose rCaIFN-γ in an open-label randomized clinical trial that tested two doses, 2000 U/kg and 5000 U/kg. The efficacy of the 5000-U/kg dose was found to be comparable to that of the 10,000-U/kg dose, whereas the 2000-U/kg dose was less effective than either of the larger doses (Yasukawa et al, 2010).
Interferons
Mode of Action
Clinical Application of Interferons in Small Animal Dermatology
Interferon-α and Interferon-β
Interferon-γ
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Chapter 40: Interferons
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