Comparison of Antiviral Immune Responses in Healthy Cats Induced by Two Immune Therapeutics
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Published on: February 2, 2014
Petra Cerna1, Steven Dow1, William Wheat1
1Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Insights
Two immune stimulants, polyprenyl immunostimulant (PI) and liposome Toll-like receptor 3/9 agonist complexes (LTCs), were compared for antiviral activity in cats. LTCs demonstrated superior interferon production, suggesting potential for managing feline infectious peritonitis (FIP).
Area of Science:
- Immunology
- Veterinary Virology
- Pharmacology
Background:
- Feline infectious peritonitis (FIP) is a significant viral disease in cats requiring effective immunotherapeutic agents.
- Current management of intractable viral diseases in cats necessitates novel immune-modulating strategies.
- Two distinct immune stimulants, polyprenyl immunostimulant (PI) and liposome Toll-like receptor 3/9 agonist complexes (LTCs), were investigated for their antiviral potential.
Purpose of the Study:
- To compare the antiviral efficacy of PI and LTC in stimulating feline immune responses.
- To evaluate the ability of PI and LTC to induce type I (IFN-α, IFN-β) and type II (IFN-γ) interferon production in vitro.
- To assess the in vivo effects of PI and LTC treatment on immune responses in healthy cats.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from healthy cats were stimulated with PI and LTC in vitro.
- Gene expression of cytokines (IFN-α, IFN-γ, IL-1β) was analyzed using RT-PCR and ELISA assays.
- Antiviral activity was assessed by measuring inhibition of Feline Coronavirus (FIPV) replication in a feline macrophage cell line.
Main Results:
- Both PI and LTC upregulated IFN-α, IFN-γ, and IL-1β gene expression in cat PBMCs in vitro.
- LTC treatment resulted in significantly higher expression of IFN-α and IFN-γ compared to PI.
- In vivo studies showed that LTC administration led to greater increases in IFN-α, IFN-γ, and IL-1β mRNA levels in healthy cats.
Conclusions:
- Both PI and LTC protocols demonstrated immune-enhancing effects beneficial for managing chronic infectious diseases like FIP.
- Activation of Toll-like receptor (TLR) 3 and 9 pathways via LTC induced broader and more potent interferon production compared to TLR 2 and 6 activation by PI.
- LTC shows promise as a therapeutic agent for enhancing antiviral immunity in cats.
Background:
Effective immunotherapeutic agents for use in cats are needed to aid in the management of intractable viral diseases, including feline infectious peritonitis (FIP) infection. The objectives of this study were to compare two different immune stimulants for antiviral activity in cats: (1) TLR 2/6-activating compound polyprenyl immunostimulant; (PI) and (2) liposome Toll-like receptor 3/9 agonist complexes (LTCs) to determine relative abilities to stimulate the induction of type I (IFN-α, IFN-β) and type II (IFN-γ) interferon immune responses in vitro and to study the effects of treatment on immune responses in healthy cats.
Methods:
Cytokine and cellular immune responses to PI and LTC were evaluated using peripheral blood mononuclear cells (PBMCs) from healthy cats incubated with LTC and PI at indicated concentrations using reverse transcriptase polymerase chain reaction assays and ELISA assays. The effects of the immune stimulants on inhibiting FIPV replication were assessed using a feline macrophage cell line (fcwf-4). Cytokine and cellular immune responses to PI and LTC were evaluated in blood samples from healthy cats treated with PI and LTC, using reverse transcriptase polymerase chain reaction (RT-PCR) and ELISA assays.
Results:
In the in vitro studies, both compounds triggered the upregulated expression of IFN-α, IFN-γ, and IL-1β genes in cat PBMC, whereas treatment with LTC induced significantly greater expression of IFN-α and IFN-γ on Day 1 and IL-1b on Day 3. There was significant protection from FIPV-induced cytopathic effects when fcwf-4 cells were treated with conditioned medium from LTC-activated leukocytes. In the healthy cat study (in vivo), both PI and LTC increased the mRNA signal for IFN-α, IFN-γ, and IL-1β above baseline at multiple time points with statistically greater increases in the LTC group on either Day 1 (IFN-α, IFN-γ) or Day 3 (IL-1β). In addition, RANTES increased over time in cats treated with the LTC.
Conclusions:
Both LTC and PI protocols induced immune-enhancing effects, suggesting a possible clinical use for the management of chronic infectious diseases like FIP. Activating the TLR 3 and 9 pathways (LTC) induced superior broad interferon production in vitro than the activation of the TLR 2 and 6 pathways (PI).
