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  • Recombinant feline interferon omega therapy in cats naturally infected with Feline Immunodeficiency Virus : clinical, viral and immunological relevance
    Publication . Leal, Rodolfo Assis Oliveira; Gil, Solange Judite Coelho Alves; Niza, Maria Manuela Grave Rodeia Espada; Tavares, Luís Manuel Morgado
    Type-I Interferons are well-known cytokines which among their main functions are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various diseases such as retroviral infections. Recombinant feline interferon omega (rFeIFN-ω) is the first interferon licensed for use in veterinary medicine. Although it is commonly administered in retroviral infections, namely in Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) infected cats, few studies reported its clinical benefits and mechanisms of action. This thesis aims to clarify the main properties of the licensed rFeIFN-ω protocol (3 cycles of 5 daily subcutaneous administrations of 1MU/kg beginning on days 0, 14 and 60) in naturally retroviral infected cats living in an animal shelter, evaluating its effect not only on clinical improvement but also on concurrent viral excretion, viremia/proviral load and various immune biomarkers such as acute phase proteins and cytokine profile. Recognizing the non specific and subtle clinical presentation of the majority of FIV-infected cats, this work also presents and evaluates an alternative oral rFeIFN-ω protocol (0.1MU/cat during 90 days) to be used in client-owned FIV-infected cats. Results showed that the licensed rFeIFN-ω protocol induces a significant clinical improvement, with a concurrent reduction of opportunistic viral infections and an increase on acute phase proteins (APP) profile. The alternative protocol also revealed an important clinical improvement but without significant changes on opportunistic viral infections (which were of low level in the tested group) or on APP profile. In both protocols, no changes were remarked on viremia neither on T-helper 1/T-helper 2 cytokine profiles meaning that this compound may lack an anti-viral activity for retroviruses in vivo and do not act on the acquired immune response of FIV-positive cats. However, there was a significant reduction of the interleukin-6 plasma levels (pro-inflammatory cytokine) in cats treated with the licensed protocol and a decrease on its mRNA expression in cats treated orally. This shows that rFeIFN-ω can have anti-inflammatory properties, which are more evident in the higher doses of the licensed protocol. More than contributing for a better knowledge of rFeIFN-ω, this thesis explores its immune modulation properties and validates a new oral protocol which can be included on future FIV-guidelines.
    2014-10-10Doctoral thesis Open access Show more