Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega

Abstract

This study assesses viremia, provirus and blood cytokine profile in naturally FIV-infected cats treated with two distinct protocols of interferon omega (rFeIFN-ω). Samples from FIV-cats previously submitted to two single-arm studies were used: 7/18 received the licensed/subcutaneous protocol (SC) while 11/18 were treated orally (PO). Viremia, provirus and blood mRNA expression of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12p40, Interferon-γ and Tumor Necrosis Factor-α were monitored by Real-Time qPCR. Concurrent plasma levels of IL-6, IL-12p40 and IL-4 were assessed by ELISA. IL-6 plasma levels decreased in the SC group (p = 0.031). IL-6 mRNA expression (p = 0.037) decreased in the PO group, albeit not sufficiently to change concurrent plasma levels. Neither viremia nor other measured cytokines changed with therapy. Proviral load increased in the SC group (p = 0.031), which can be justified by a clinically irrelevant increase of lymphocyte count. Independently of the protocol, rFeIFN-ω seems to act on innate immunity by reducing pro-inflammatory stimulus.

Interferon-omega: Current status in clinical applications

“…Specifically, IL-6 plasma levels decreased and proviral loads increased in FIV-cats treated subcutaneously with rFeIFN-ω, while IL-6 mRNA expression decreased in the oral group. However, the therapy did not affect viremia and the expression of other cytokines (IL-1, IL-4, IL-10, IL-12p40, IFN-γ, and tumor necrosis factor-α) [49]. Thus, IFN-ω appears to be involved in innate immunity, and it could further inhibit viral replication and exert its antiviral activity.…”

“…When cells are treated with IFN-ω, Mx-1, ISG15, IFIT3, and ISG56 expression was upregulated in a dose-dependent or time-dependent manner [20,29]. More recently, studies from Leal et al [49] showed that interleukin (IL)-6 production was affected considerably in feline immunodeficiency virus (FIV)-infected cats treated with recombinant feline IFN-ω (rFeIFN-ω) by subcutaneous or oral protocols. Specifically, IL-6 plasma levels decreased and proviral loads increased in FIV-cats treated subcutaneously with rFeIFN-ω, while IL-6 mRNA expression decreased in the oral group.…”

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

“…IL-6 mRNA expression decreases in an oral group. Viremia and other cytokines (IL-1, IL-4, IL-10, IL-12p40, IFN-γ and TNF-α) do not change with therapy [75]. A previous study showed that cytotoxic effects (e.g.…”

“…These results indicate that the two protocols are probably acting distinctly. Th-1 and Th-2 responses do not significantly change with either protocol, and only levels of IL-6, a pro-inflammatory cytokine involved in different immune pathways, particularly the innate immune response, significantly change in both groups [75]. In cats treated with the licensed protocol, IL-6 plasma levels are significantly reduced.…”

“…In cats treated with the licensed protocol, IL-6 plasma levels are significantly reduced. Treatment with oral rFeIFN-ω did not change IL-6 plasma levels, but concurrent mRNA expression significantly decreased [75]. These results indicate that rFeIFN-ω has anti-inflammatory properties and higher pulsate therapy is more available than continuous low dose therapy for decreasing pro-inflammatory stimuli [75].…”