Because it can decrease both T H1 and T H2, TGF-β is most commonly associated with tolerance and is found in high levels in the intestine and lungs, where large doses of innocuous antigens are frequently introduced. This cytokine was discovered through its ability to increase the growth of tumor cells, mediated by decreasing the T H1 response. While many categories of Treg cells exist, most Tregs produce TGF-β (transforming growth factor β). Regulation of the T-cell response is accomplished by Treg cells, also called T H3 or Treg cells. Thus, a T H2 response can be detrimental to cancer patients because it decreases IFN-γ and decreases the cellular immune response to cancer. IFN-γ decreases production of IL-4, and IL-4 decreases production of IFN-γ. Most important, IL-4 and IFN-γ cross-regulate each other. T H2 responses are associated with allergies and asthma and involve the cytokines IL-4, IL-5, IL-13, and sometimes IL-10. In contrast to a T H1 response, a T H2 response is not typically associated with an immune response to cancer. Thus, therapies, including use of mushrooms that increase IFN-γ and drive a T H1 response, are beneficial for cancer patients. In addition, a number of cellular functions, such as presentation of tumor-specific antigens and production of tumoricidal cytokines, are increased by IFN-γ. Cellular immunity is important in an antitumor response since NK and CD8+ T cells, as well as tumoricidal macrophages, can destroy tumor cells. The dominant T H1 cytokine is IFN-γ, which is responsible for stimulating the cellular immune response. The cytokine pattern associated with a beneficial immune response to cancer is T H1.
To evaluate the role of cytokines in disease, it is necessary to evaluate several cytokines from each pathway because the overall pattern may have a larger impact on the body than any individual cytokine. Cytokines are cross-regulatory, and the expression of one pattern of cytokines can modulate other cytokine patterns. Each of these defined patterns can have a different physiological effect in a cancer patient ( Table 2). Patterns of importance in cancer research include T H1, T H2, T H3/T regulatory (Treg) cells, and the proinflammatory pathways. The cytokines involved in different types of responses are defined as cytokine patterns. In the effort to understand cytokine responses and the interrelationships between cytokines, one approach has been to characterize a certain set of cytokines for responses to different situations. Cytokines are small, soluble proteins that act as intracellular mediators in an immune response.
One of the myriad effects of mushrooms occurs through their ability to stimulate cytokine production. The most common medicinally active ingredient among mushrooms is β-glucan. Many of the compounds studied have yet to be named and are often referred to by gel chromatography fraction when they are studied. The 5 mushrooms explored in this paper have many active constituents including, but not limited to, polysaccharides, polysaccharide peptides, proteins, terpenoids, and nucleotides ( Table 1). The common and scientific names of the mushrooms discussed in this article are found in Table 1. The fruiting body grows off the hyphae and produces spores for reproduction ( Figure 1). The fungal body can be a single cell or a structure called a hypha or mycelial threads. Mushrooms represent a unique branch of botanical medicine and are classified in the kingdom of Fungi. Additionally, evidence suggests that medicinal mushrooms may safely boost chemotherapeutic efficacy and simultaneously protect against bone marrow suppression. 1 Extensive research over the last 40 years has demonstrated that mushrooms have potent antineoplastic properties that slow growth of tumors, regulate tumor genes, decrease tumoral angioneogenesis, and increase malignant-cell phagocytosis. It is well-established that mushrooms are adept at immune modulation and affect hematopoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and natural killer (NK) cells.
Mushrooms are reported to have antimicrobial, anti-inflammatory, cardiovascular-protective, antidiabetic, hepatoprotective, and anticancer properties. They have been used medicinally since at least 3000 bce. Medicinal mushrooms have been proposed as a novel therapy that may improve cancer treatment and patients’ survival.
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