Interferon

Veterinary Immunology and Immunopathology 109 (2006) 245–254 www.elsevier.com/locate/vetimm

Low-dose interferon-a treatment for feline immunodeficiency virus infection
E. Pedretti a, B. Passeri b, M. Amadori a,*, P. Isola c, P. Di Pede d, A. Telera d, R. Vescovini d, F. Quintavalla b, M. Pistello c
Department of Animal Welfare and Immunoprophylaxis, Istituto Zooprofilattico Sperimentale, viaA. Bianchi 9, 25124 Brescia, Italy b Department of Animal Health, Faculty of Veterinary Medicine, via del Taglio 8, 43100 Parma, Italy c Department of Experimental Pathology, Retrovirus Center and Virology Section, University of Pisa, via San Zeno 35, 56127 Pisa, Italy d Department of Internal Medicine and Biomedical Sciences, Faculty of Medicine, via Gramsci 14, 43100 Parma, Italy Received 22March 2005; received in revised form 12 July 2005; accepted 15 August 2005
a

Abstract Feline immunodeficiency virus sustains an AIDS-like syndrome in cats, which is considered a relevant model for human AIDS. Under precise enrolment requirements, 30 naturally infected cats showing overt disease were included in a trial of lowdose, oral human interferon-a treatment. Twenty-four of them received 10IU/Kg of human interferon-a and 6 placebo only on a daily basis under veterinary supervision. The low-dose human interferon-a treatment significantly prolonged the survival of virus-infected cats ( p < 0.01) and brought to a rapid improvement of disease conditions in the infected hosts. Amelioration of clinical conditions was neither correlated with plasma viremia, nor with proviral load inleukocytes. A good survival of CD4+ T cells and a slow increase of CD8+ T cells were also observed in human interferon-a-treated cats. Interestingly, the improvement of the total leukocyte counts showed a much stronger correlation with the recovery from serious opportunistic infections. As shown in other models of low-dose interferon-a treatment, there was a rapid regression of overt immunopathologicalconditions in virus-infected cats. This hints at a major role of interferon-a in the control circuits of inflammatory cytokines, which was probably the very foundation of the improved clinical score and survival despite the unabated persistence of virus and virusinfected cells. # 2005 Elsevier B.V. All rights reserved.
Keywords: Interferon-a; Feline immunodeficiency virus; Feline AIDS; Cats

1.Introduction
* Corresponding author. Tel.: +39 030 2290349; fax: +39 030 2290382. E-mail address: mamadori@bs.izs.it (M. Amadori).

In vivo experiments of low-dose, oral interferon-a treatment have been described in many animal species

0165-2427/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2005.08.020

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E. Pedretti et al. / Veterinary Immunologyand Immunopathology 109 (2006) 245–254

(e.g. humans, cattle, pigs, horses) (Cummins et al., 2005). Such a treatment was shown to induce dramatic clinical amelioration in models of both infectious and chronic inflammatory and/or autoimmune diseases (Tompkins, 1999). The majority of these findings refer to the use of different preparations of human interferona (hIFN-a), which shows widecross-reactivity with cells of other animal species (Viscomi, 1997). Human IFN-a at the applied low oral doses (1–10 IU/kg body weight) cannot exert direct antiviral activity in vivo of any importance, because of the proteolytic digestion in the gastrointestinal tract (Cummins, 2005). Human IFN-a strengthens instead the immune response to viral infections, with a significant modulation of important cytokineslike IL-1, IL-5, IL-6, IL-8, GM-CSF (Naylor et al., 1999; Tompkins, 1999). The favourable effects of low-dose, oral, natural hIFN-a treatment were also confirmed in feline leukemia virus (FeLV)-infected cats, which showed longer survival than placebo-treated animals (Cummins et al., 1988; Weiss et al., 1991). Oral treatment with recombinant hIFN-a was of some clinical benefit to both FeLV and...