Researchers at Colorado State University discovered that VetIMMUNE® PI upregulates the protective immune response by triggering the production of interferon-γ (IFN-γ), even in healthy kittens.
This post marks the beginning of a series that describes how VetIMMUNE® PI (formerly known as Polyprenyl Immunostimulant) works to enhance protective innate immune responses. One of the mechanisms is linked to the function of cytokines, including interferons; therefore, I will start with a brief primer on those.
Everybody has heard about interferons, and some of our readers received them as part of medical protocols. Interferons (IFNs) are a subgroup of cytokines, signaling proteins synthesized by cells in response to the presence of viruses, pathogens, or abnormal cells (like cancer). They are denoted with Greek letters after the word "interferon" and are subdivided into three types, e.g., Type I (IFN-α and β), Type II (IFN-γ), and Type III (IFN-λ). All IFNs are key regulators of the complex network of immune responses within organisms. IFN-α and β primarily focus on antiviral defense, while IFN-γ activates immune cells responsible for pathogen destruction. Additionally, IFN-λ regulates immune response in the mucosa of the respiratory system, gut, and other organs. All organisms can produce these molecules, but pathogens strive to evade or neutralize the interferons.
My personal interest lies in IFN-γ, a multifunctional cytokine, a signal molecule produced by T- and natural killer (NK) cells, which act as a radar in surveillance when they detect an assault (pathogen). In its turn, IFN-γ, the signal, triggers multilayered defense actions that lead to the destruction of the invading virus. The sequence of events is similar to any battlefield: surveillance systems detect the threat and send a signal to defense systems. The attacking party tries to destroy the surveillance systems and the defense. I will launch the series by discussing IFN-γ and VetIMMUNE® PI.
From my previous post about Dr. Elie Metchnikoff, you are aware of how he discovered macrophages, immune cells that engulf and destroy pathogens. IFN-γ activates macrophages; for example, it serves as a signal that alerts macrophages to be ready to respond to pathogen assault. (While pathogens do everything possible to evade or destroy the macrophage before it sees them). Macrophages are a part of the cellular immune response; they act fast. They are the first line when antibodies are weak or absent.
When alerting macrophages, IFN-γ also enhances and upregulates other parts of the cell-mediated immune response by T lymphocytes and other immune cells. At the same time, a deficiency in IFN-γ leads to an increased susceptibility to infections (image credit https://www.science.org/doi/10.1126/science.adl2016). For the past 50 years, it has been used in human medicine to treat a variety of chronic viral infections, such as hepatitis B and C, HIV, and others.
Of course, enhancing the body's own natural IFN-γ and having it ready to launch the cellular immune response to infections is a dream come true. Drs. Petra Cerna, Steve Dow, Lyndah Chow, Jennifer Hawley, and Michael Lappin, researchers of Colorado State University, discovered the ability of VetIMMUNE® PI to enhance IFN-γ production even in healthy kittens. They published their discovery last year (Cerna et al., 2024), and you are welcome to download it through the link here: https://vetimmune.com/pages/about-vetimmunepi (scroll to the bottom of the page for the list). The paper reports other important discoveries, which I will review later. Here's to IFN-γ!
Researchers worked with healthy kittens from the university colony. The kittens were not harmed during the study and remained alive and well afterward; the researchers observed no adverse effects of VetIMMUNE® PI.
The researchers experimented, mimicking what happens to blood immune cells after a healthy kitten receives VetIMMUNE® PI. They drew blood from healthy kittens and isolated peripheral blood mononuclear cells (PBMC), the blood cell population comprising T-, B-, NK (natural killer) cells, and monocytes. These cells are involved in immune surveillance and alert to pathogens. Some of those cells belong to "the lymphoid cell subsets" in the picture above.
The PBMCs were incubated with a placebo (negative control), a positive control (LPS), and VetIMMUNE® PI at different concentrations (1 μL per well, 0.3 μL per well, and 0.1 μL per well) and tested after 24 h using standard commercially available ELISA kits and scientific instruments, which are set to detect IFN-γ.
The negative control indicates what happens to the cells in the absence of VetIMMUNE® PI and serves as a baseline for comparison to the effect. The positive control, with a known trigger, is set to demonstrate that the cells are live and active and respond as expected.
The figure (after Cerna et al., 2024) shows that VetIMMUNE® PI enhanced the natural IFN-γ production by the "disease surveillance subset" of blood immune cells. The cats were healthy, meaning that VetIMMUNE® PI helps maintain a healthy level of the protective cellular immune response when IFN-γ production may be insufficient!
Note that higher concentrations of VetIMMUNE® PI triggered higher concentrations of IFN-γ compared to untreated cells, with statistical probability scores p ≤ 0.001 (****) for 100 μl/ml and p ≤ 0.01 (**) for 10 μl/ml (lower scores denote higher statistical probability).
This discovery is significant because it proves that VetIMMUNE® PI supports the protective immune response through one of the fundamental mechanisms – triggering IFN-γ production.
This discovery shows that if a pet has an immune response that is naturally weak at an early age or later in life, or is affected by stress or pathogens, VetIMMUNE® PI will enhance the immune response by triggering IFN-γ to healthy levels, giving the pet a gift of health, quality of life, and longevity.
