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Beta Glucans in the Immune System | OraMune

WHAT IS BETA 1,3/1,6-D-GLUCAN?

Beta glucans are extracted from the common baker's yeast Saccharomyces cervislae and composed of chains of 20-30 glucose units with side chains of beta 1,3 and beta 1,6 linked D-glucose molecules. The overall effect is that of a tree with a trunk, and conditions to yield pure glucans with their unique structures preserved for maximum interaction and activation of immune cells. These products contain no yeast cells, are completely safe and have no toxic side effects.

HOW BETA GLUCANS ACTIVATE THE IMMUNE SYSTEM?

In the 1960's Nicholas DiLuzio and his collaborators published a number of papers that described the broad spectrum anti bacterial and tumor inhibitory activity of beta glucans. These observations were attributed to augmented host immune defense by mechanisms involving macrophage or phagocyte activation. Phagocytes (monocytes, macrophages, granulocytes), natural killer cells, dendritic cells, and langrehans cells of skin bear specific receptor sites termed dectin-1 (betaGR) that bind beta 1,3 and or beta 1,6 glucans. Phagocytes also express a whole range of receptors that recognize and bind to foreign invaders, such as microbes, viruses, yeasts, parasites and possibly even neoplastic cells. Binding to certain organisms is also facilitated by recognizing serum opsonins or antibodies that have been deposited on their surface. Once the cell receptor binds beta glucans, immune activity is initiated. Activated macrophages undergo morphologic and physiologic changes that result in enhanced phagocytic (scavenger) activity, release certain cytokines or hormone messengers that engage both innate and acquired immune system (see transfer factor). Such cytokines as tumor necrosis factor alpha, interleukin-1 beta and granulocyte – macrophage colony stimulating factor and others profoundly affect local and systemic immunity.

IMMUNO-PHYSIOLOGIC EFFECTS OF BETA GLUCAN ADMINISTRATION

Host Immune Response:

The administration of purified yeast glucan to a host rapidly results in an augmented state of hose resistance to a diverse range of microbial pathogens and possibly neoplastic cells. Prior to establishment of such resistance, surface receptors, Dectin-1 on macrophages, monocytes neutrophils, dedritic cells and subpopulation of T cells recognize and bind beta glucan. Lung (alveolar) macrophages, like inflammatory macrophages exhibit the highest surface expression of Dectin-1 (beta GR) glucan receptor and provide an important mechanism for internalization and clearance of particulate pathogenic targets. This indicates a role for the receptor in immune surveillance and control of disease. Yeast type beta glucans are also potent biologic response modifiers. They markedly augment host resistance to a variety of biologic insults by eliciting a cascade of stimulatory events initiated by mononuclear phagocytes. Upon interaction and binding of beta glucan, macrophages produce bactericidal compounds like Iysozyme, reactive oxygen radicals and nitric oxide. In addition, these cells start producing a number of inflammatory cystokines that will interact with the surrounding macrophages and lymphocytes to initiate local and acquired specific immunity. Some of these cytokines are interleukin-1, interleukin-6, and tumor necrosis factor alpha.

Interleukin-1:

Upon binding and phagocytosis of glucan by macrophages, these cells release interleukin-1 (IL-1) an immune systems messenger. IL-1 alpha and IL-1 beta are two similar polypeptides involved in inflammatory reactions.

Interleukins-6:

Interleukins-6 is a multifunctional protein that plays important roles in host defense, acute phase reactions, immune response and hematopoiesis or production of blood cells.

Tumor Necrosis Factor Alpha:

Under experimental conditions, mice administered beta glucan produce tumor necrosis factor (TNF-alpha) in their peritoneal macrophages. Similarly human monocytes stimulated with beta glucan in culture produce TNF-alpha. Studies implicate binding of Dectin-1 the macrophage receptor in production of TNF-alpha, a critical step required for the successful control of many pathogens.

Effect of beta glucan On Antibiotic Therapy:

Beta glucan redness need and potentiates antibiotic therapy. When beta glucan was added to antibiotic regimen in animals challenged with different bacterial and fungal pathogens (Stahpylococcus aureus, kiebsiella pneumoniae, Escherchia coli, Candida albicans and others) or viral pathogens such as herpes and murine viral hepatitis, a reduced amount of antibiotics or antivirals were needed to cope with the infection.

Effect of beta glucan on Immune Deficiency:

In certain cases of virally induced immune deficiency, beta glucan ameliorated the infectious process in these patients possible by mounting a direct assault against the indigenous viral infection or by mechanisms referred to above preventing over growth of opportunistic pathogens.

Effect of beta glucan on radiations:

Under experimental conditions, rodents exposed to lethal and sub-lethal irradiation and administered beta glucan had significantly larger number of survivors. These observations were attributed to the fact that beta glucan is a potent free radical scavenger that protects blood macrophages from free radical attack after radiation exposure thus ensuring immune function. Additionally administration of beta glucan enhanced hemopoietic reconstitution and stimulated production of blood stem cells thus preventing septicemia and resistance to enteric opportunistic pathogens.

Effect of beta glucan on Chemotherapy:

Chemotherapy may induce immune suppression and result in subsequent infection with opportunistic infections. Such life threatening conditions may be averted by administration of beta glucan. Leukocytopenia is a decrease in the number of white blood cells due to chemotherapy. Consequently lower dosages of drugs are used which comprise the curative effect of chemotherapy. However, with beta glucan, white blood cell depletion may be avoided in experimental animals. In another experimental model, combination of beta gulcan and interferon-gamma demonstrated synergistic therapeutic effect. Similarly superior synergistic potential of beta glucan in combination with radiation and chemotherapy were reported.

Effect of beta glucan on Wound Healing:

The effectiveness of yeast glucan on acceleration of wound healing was evaluated in several experimental animal models. In every instance, animals treated with beta glucan showed more advanced healing. The histological analysis showed that the acceleration of wound healing was mediated by early arrival of macrophages to the wound area in the glucan treated animals.

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