Immunomodulation Properties of Mistletoe Extracts
The immune system provides the body’s defence against external intruders, which is a network of cells, tissues, and organs. The immune system is always searching for poisons, viruses, and bacteria that do not belong in the body. An immunological reaction is triggered when the immune system recognizes something foreign (Oei et al., 2019). The immune response is a complex process that includes several varieties of cells and proteins. The skin and mucous membranes are the first lines of defence against foreign invaders. These barrier tissues prevent most microbes from entering the body. If a microbe does manage to get past the barrier tissues, the immune system is ready to fight back. The immune system can recognize foreign invaders through a process called antigen recognition. Antigens are molecules found on the surface of bacteria, viruses, and other foreign invaders. The immune system has special proteins called antibodies that recognize antigens.
When an antibody binds to an antigen, it triggers a chain reaction that leads to the destruction of the foreign invader. The first step in this process is called activation. Activation occurs when an antigen binds to an antibody on the surface of a white blood cell. This binding triggers a series of chemical reactions that cause the white blood cell to change shape and release chemicals that attract other white blood cells to the site of infection (Oei et al., 2019). The second step in the immune response is called proliferation. Proliferation is the process by which the immune system produces more white blood cells to fight the infection. The body produces two types of white blood cells: lymphocytes and phagocytes. The third step in the immune response is called elimination. Elimination is the process by which the immune system gets rid of the foreign invader (Noryśkiewicz & Noryśkiewicz, 2017). The body gets rid of foreign invaders in two ways: by destroying them or by removing them from the body.
Photo (Mistletoe-therapy.org, 2022).
A form of cancer treatment known as cancer immunotherapy uses the immune system’s ability to combat cancer cells. The immune system is a sophisticated mechanism made up of several varieties of cells and proteins that cooperate to defend the body against sickness and infection. Cancerous cells are aberrant cells that can infect neighbouring tissues and develop out of control. Cancer cells can occasionally evade the immune system’s ability to detect them, even though it is meant to identify and eliminate them. Cancer immunotherapy employs agents that support the immune system’s ability to detect and eliminate cancer cells. Cancer immunotherapy works by urging the immune system to hunt for and eliminate cancer cells actively.
There are many different types of cancer immunotherapy, and each works differently. Some types of cancer immunotherapy are used to boost the body’s natural immune response, while others are designed to target cancer cells specifically. Monoclonal antibodies: Monoclonal antibodies are artificial versions of antibodies created in a laboratory. They are designed to recognize and bind to specific proteins on the surface of cancer cells (Mistletoe-therapy.org, 2022). Once the monoclonal antibody binds to the cancer cell, it can help the immune system to kill the cancer cell. Cytotoxic T-lymphocytes: Cytotoxic T-lymphocytes are a type of white blood cell that can kill cancer cells. They are often combined with other immunotherapy types, such as monoclonal antibodies. Interleukin-2: Interleukin-2 is a protein that helps to regulate the immune system. It is often used in combination with other types of immunotherapy, such as cytotoxic T-lymphocytes (Noryśkiewicz & Noryśkiewicz, 2017). Cancer vaccines: Cancer vaccines are designed to stimulate the immune system to recognize and kill cancer cells. They are made from pieces of the cancer cells or proteins found on the surface of cancer cells.
Cancer immunotherapy is still in the early stages of development, and many questions have yet to be answered about how it works and how well it works. However, cancer immunotherapy is already showing promise as a treatment for many different types of cancer, and it is likely to become an important part of cancer treatment in the future.
Immunomodulation properties of mistletoe extracts
Photo (Anna, 2019)
Triterpenoids, flavonoids, alkaloids, and polysaccharides are only a few substances found in mistletoe extracts that influence the immune system. The triterpenoid Viscum album 3-beta-D-glucopyranoside (VAG), which is present in all mistletoe preparations, is the most researched. It has been demonstrated that VAG increases the development of several crucial immune cells, including dendritic cells, macrophages, and natural killer cells. The production of cytokines, including interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), has also been demonstrated to rise in response to VAG (Mistletoe-therapy.org, 2022). The development of a powerful immune response depends on these cytokines. Additionally, VAG increases the expression of several immune-related genes, including those that code for Toll-like receptors (TLRs).
Pattern-recognition receptors, known as TLRs, are important for the innate immune response. They can identify harmful microbes and start an immune reaction. VAG upregulates TLR genes suggesting that mistletoe extracts can support the innate immune response. VAG has been demonstrated to have anti-cancer qualities in addition to its immunomodulatory actions. It has been demonstrated to stop the development of several cancer cell types, including lung, colon, and breast cancer cells. VAG has also been demonstrated to cause cancer cells to undergo apoptosis.
Effects on cells of the non-specific immune system
According to current scientific studies, mistletoe extracts can affect the non-specific immune system’s activity, albeit the precise processes by which this happens are still not entirely known. The physiologically active substances in mistletoe extracts include lectins, alkaloids, flavonoids, and terpenoids. The immune system’s many cell types, such as macrophages, dendritic cells, natural killer cells, and T and B lymphocytes, are hypothesized to interact with these substances.
The potential of mistletoe extracts to enhance macrophage activity is one of the most well-researched immunomodulatory effects. White blood cells, known as macrophages, are important for the body’s innate immune response (Mistletoe-therapy.org, 2022). They can phagocytose (engulf and kill) invasive pathogens and release a range of cytokines that assist in controlling the immune response. Tumour necrosis factor (TNF) and interleukin (IL)-1 are two pro-inflammatory cytokines that macrophages can produce when exposed to mistletoe extracts, according to in vitro research (5, 6). These cytokines are crucial to the body’s response to infection and aid in attracting other immune cells to the infection site.
Mistletoe extracts have been found to boost the activity of natural killer (NK) cells in addition to their actions on macrophages. White blood cells, known as NK cells, are important for the body’s innate immune response to viral infections (Gardin, 2018). They can eliminate virally-infected cells and aid in limiting viral infection spread. Mistletoe extracts have been proven in vitro experiments to increase NK cell production of interferon (IFN)- (8). A crucial part of the body’s reaction to viral infections is played by the cytokine IFN-. It supports the generation of antiviral proteins and the activity of other immune cells.
Mistletoe extracts have been demonstrated to affect the activity of the hypothalamic-pituitary-adrenal (HPA) axis and their direct actions on immune cells. A crucial part of the body’s stress response mechanism is the HPA axis. In reaction to stressful circumstances, it is in charge of releasing stress hormones like cortisol. Mistletoe extracts can prevent the adrenal gland from releasing stress hormones, according to in vitro and animal research. The lectin component of mistletoe extracts, which binds to adrenocorticotropic hormone (ACTH) and prevents its release from the pituitary gland, is likely to be the mechanism causing this action.
Effects on cells of the specific immune system
It has been demonstrated that mistletoe extracts affect a certain immune system’s cells. The extracts expose the immune system to foreign antigens, which triggers a certain lymphocyte proliferation. ML I was initially primarily responsible for this induction of a particular immunological response. However, it is now understood that ML II, ML III, or viscotoxins can also increase cell proliferation and antibody production (Gardin, 2018). Both cancer patients receiving mistletoe treatment and healthy volunteers who received mistletoe extracts over a longer time develop these antibodies. Although the anti-ML I and anti-ML III antibodies may occasionally also be of the IgE isotype, the antibodies are primarily of the IgG isotype (IgG1 and IgG3). Later, mistletoe extracts were used to identify another lectin, the so-called chitin-binding mistletoe lectin (cbML). When cancer patients and healthy volunteers get mistletoe treatment, antibodies against this lectin that are only of the IgG class are also induced.
In vitro exposure of lymphocytes to cbML also increased proliferation. It was an intriguing finding that antibodies against cbML could also be found in people who had never come into contact with mistletoe extracts. In contrast, only those who have come into contact with mistletoe extracts have immune responses to ML I, III, or viscotoxins. Cross-reactions are most likely to blame for this.
Human case studies
A clinical trial involving 43 healthy volunteers showed that the number of leukocytes, granulocytes, and eosinophil cells rose immediately after a subcutaneous VA injection. Additionally, the effect of VA extracts on T-lymphocyte functioning was investigated. It was shown that subcutaneous applications of VA extracts caused eosinophilia and an increase in CD4 T-lymphocytes in a placebo-controlled experiment with 71 healthy participants. Eight cancer patients participated in a clinical investigation where VA extracts were applied, and the blood cytokine levels rose as a result (Gardin, 2018). Activation of natural killer (NK) and T-helper cells was seen following subcutaneous injections of VA lectins in other clinical research with ten breast cancer patients.
Experiments with mouse vaccinations demonstrated the effectiveness of lectins as immunoadjuvants to boost cellular and humoral immune responses. Korean mistletoe lectins showed immunomodulatory capabilities by promoting dendritic cell maturation in research using cultivated tumour cells. In an in vitro experiment employing a human cellular system, administering VA extracts can induce maturation in human dendritic cells.
Mistletoe therapy can serve as an immunomodulatory agent in the fight against cancer. The plant-based drug has been shown to stimulate the immune system, specifically the production of cytokines and natural killer cells. These cells are important in the destruction of cancer cells. Additionally, mistletoe therapy has been shown to reduce the side effects of chemotherapy and radiation therapy. These side effects can be debilitating and often prevent patients from completing their treatment. Reducing side effects allows patients to tolerate their treatment better and increases the likelihood of a successful outcome.
Anna, S. (2019). Retrieved 11 October 2022, from https://www.researchgate.net/figure/Mechanism-of-anticancer-activity-of-mistletoe-Mistletoe-targets-two-important-signalling_fig1_342682914.
Gardin, N. (2018). Immunological response to mistletoe (Viscum albumL.) in cancer patients: a four-case series. Phytotherapy Research, 23(3), 407–411. https://doi.org/10.1002/ptr.2643
Oei, S., Thronicke, A., & Schad, F. (2019). Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies. Evidence-Based Complementary And Alternative Medicine, 2019, 1-6. https://doi.org/10.1155/2019/5893017
Mistletoe-therapy.org. (2022). Mistletoe therapy: Immunomodulating properties. Mistletoe-therapy.org. Retrieved 10 October 2022, from https://www.mistletoe-therapy.org/scientific-information/constituents-and-mode-of-action/immunomodulating-properties.
Noryśkiewicz, A., & Noryśkiewicz, B. (2017). Remarks on Pollen Representation of Mistletoe (Viscum album L.). Ecological Questions, 26, 19. https://doi.org/10.12775/eq.2017.011Tags: Blog, cancer immunomodulation, cancer immunotherapy, cancer research, immunomodulation properties, mistletoe, mistletoe extracts