Environmental Pollutants and Immunity

The immune system is particularly vulnerable to toxic pollutants. Numerous herbicides plus pesticides, fungicides and insecticides impact normal immune function, both in animals as well as in humans. A pesticide is any substance used to kill, repel or control unwanted insects or animals that are considered to be pests. Hundreds of pesticides are used regularly, and only a fraction have been tested for safety. Humans are exposed to herbicides and pesticides through their diets due to widespread agricultural use, as well in homes, schools and workplaces. Many of these toxic chemicals include ingredients that persist in the environment, meaning that they do not breakdown over time. This allows them to accumulate to levels that can cause physiological damage and result in disease. Although toxic environmental chemicals have been shown to cause numerous adverse physiological changes including hormonal abnormalities, reproductive difficulty, DNA damage, liver and kidney disease, and many others, this article will focus on the immunological impacts of these chemicals.

Table 1. The Twelve Foods With Highest Pesticide Residues
•  Peach
•  Bell Pepper
•  Nectarine
•  Cherries
•  Lettuce
•  Carrot
•  Apple
•  Celery
•  Strawberries
•  Kale
•  Grapes (Imported)
•  Pear
Source: Environmental Working Group, available at www.ewg.org

These environmental chemicals can induce numerous structural and functional changes in the immune system. Some of these changes include changes in the number and type of white blood cells (lymphocytes) and decreased function of these cells. These changes result in a reduced ability of the immune system to fight off foreign pathogens or remove cells damaged by these toxic chemicals from the body. In turn, this may result in conditions such as autoimmune disease, increased infections and allergies, and transformations of normal cells to neoplastic forms. Some researchers suggest that pesticide exposure may impact individuals with fragile immune systems more than others, which leads to increased disease susceptibility.1

There are several mechanisms proposed to explain how herbicides and pesticides cause physiological changes. These chemicals are known to induce free radicals, which cause cellular oxidative stress and DNA damage. In the immune system, this may result in damage to the white blood cells known as lymphocytes, which are important cells for killing pathogens, immunological memory, recognition of “self” vs. foreign proteins and removing abnormal cells. Research indicates that agricultural workers exposed to organophosphate pesticides have increased serum malondialdehyde, which is a marker of oxidative stress. In fact, serum malondialdehyde was 4.9 times higher in the farm workers and 24 times higher in those workers that apply the herbicides and pesticides compared to control subjects. The farm workers also had increased lymphocyte DNA damage compared to control subjects. Furthermore, the researchers showed that organophosphates induced markers of oxidative stress in the lymphocytes including the generation of increased reactive oxygen species and reduction of levels of the antioxidant glutathione.2

Another way in which these toxic environmental chemicals affect the immune system is by altering the types of cells produced and the signaling chemicals (cytokines) that are released from the cells. One study investigated the effect of several pesticides on immune function, including 2,4-dichlorophenoxyacetic acid (2,4-D), which is the most widely used herbicide in the world. The study found that 2,4-D increased the amount of immunoglobulin (Ig)-E, which plays a role in allergic reactions and asthma. Additionally, there was an increase in the chemical mediators, called interleukins, such as IL-4, IL-5, IL-10, and IL-13, which are also associated with allergic reactions.3 Similarly, another study of agricultural workers showed that pesticide exposure caused changes in levels of immune proteins as well as altered levels of the immunoglobulins IgG4 and IgA compared to control subjects.4

Another study examined the health effects of DDT, a pesticide that was banned in the United States in 1972, but is still routinely detected on foods. DDT has been shown to cause immunosuppression by altering the production of immune proteins such as increasing complement (C) proteins C3a, C3b and C3d, which results in reduced killing (lytic) functions of the immune system. DDT also altered the structure of the macrophages, which are a type of white blood cell involved in recognizing, engulfing and destroying foreign pathogens, plus increasing the production of pro-inflammatory cytokines and free radicals.5 Various other environmental chemicals have been shown to affect natural killer (NK) cells, a type of lymphocyte important for initial immune defense against tumor cells and virally infected cells, resulting in reduced lytic activity.6-7 Other research has examined the effects of propanil, which is one of the most widely used herbicides in the United States. The study found that propanil altered the immune organs, caused wasting of the thymus and enlargement of the spleen. It also caused a reduction of both T-lymphocytes and B-lymphocytes, and suppressed the killing activity of NK cells and macrophages.8

Diseases Associated with Pesticide Exposure

The immune modulation caused by environmental contaminants leads to an increased risk of several diseases including autoimmune disease, allergies, increased infections as well as neoplasms. Furthermore, environmental exposures during prenatal and early postnatal development have been linked to a growing number of childhood diseases such as allergic disorders, leukemia9 and increased upper respiratory infections.10

One study investigated the relationship between organic pollutants and arthritis. The study found that increasing levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides such as pentachlorophenol were associated with increased risk of arthritis in women. Additionally, the study found an even stronger association with rheumatoid arthritis, which is an autoimmune disease that affects the joints. The data showed an increased risk of rheumatoid arthritis of 8.5-fold in the women with the highest serum levels of dioxin-like PCBs.11

Optimizing Immune Function

Due to the widespread exposure to environmental toxins and the risk of chemically induced altered immune responses, it is imperative to optimize and protect the vital immune functions. As an antioxidant, green tea is important to neutralize the free radicals generated by pesticide exposure, and mushrooms such as Agaricus blazei, Cordyceps sinensis, Grifola frondosa (Maitake), Coriolus versicolor, Ganoderma lucidum (Reishi), Lentinula edodes (Shitake), and Cordyceps sinensis (all found in ImmuneAssist® 24/7) can support optimal immune function.

Research has shown that constituents of various mushrooms, including the polysaccharide 1-3 beta glucan, help balance immune function. The mushrooms Agaricus blazei,12 Grifola frondosa,13 and Ganoderma lucidum14 have been shown to improve natural killer (NK) cell activity, which has been shown to be reduced by herbicide and pesticide exposures. Additionally, the mushroom Coriolus versicolor has been shown to restore killer T-lymphocyte function in animals with tumors,15 as well as induce apoptosis in human leukemia cells.16 Also, research has shown that the mushroom Lentinula edodes (Shitake) can increase the ability of macrophages to engulf and destroy foreign pathogens or abnormal cells by increasing the release of cytokines that stimulate macrophage activity.17 Research also indicates that macrophage activity is suppressed with pesticide exposure.

One study showed that rats exposed to the pesticide pentachlorophenol (PCP) and subsequently supplemented with green tea resulted in the suppression of liver and gall bladder tumors when green tea was administered. The researchers stated, “These findings suggest that regular intake of green tea may reduce the carcinogenic risk posed by an environmental pollutant, PCP, presumably due to effects on oxidative stress.”18 Thus, adequate intake of the green tea polyphenol antioxidants is important.

Pesticides have been reported to induce oxidative stress due to generation of free radicals and the alteration in antioxidant defense mechanisms. Antioxidant enzymes such as superoxide dismutase and glutathione reductase have been shown to be decreased in agriculture workers exposed to pesticides.19 Other studies have shown that glutathione levels are lowered in red blood cells after exposure to organophosphates indicating increased oxidative stress.20 In addition to antioxidant activity, glutathione is also important for detoxification of herbicides and pesticides. Reduced glutathione interacts with toxic chemicals making them less reactive and thus less damaging to cells. This detoxification reaction causes the glutathione to become oxidized and to lose its antioxidant activity. Thus, glutathione must be constantly replenished for optimal removal of toxins. Furthermore, glutathione conjugation in the liver allows fat-soluble toxins to become water-soluble, which allows them to be excreted from the body in the urine. Supplementation with the liposomal-form of glutathione allows for increased absorption and protects the glutathione so it remains in the reduced or active state.21

Conclusion

The widespread use of herbicides and pesticides makes it difficult for even the most health-conscious individuals to avoid them completely. These environmental chemical contaminants can damage the immune system and increase the risk of several immune-related diseases, including allergies, autoimmune disease and neoplasms. Thus, supporting the immune response with both medicinal mushrooms and antioxidants, such as glutathione and green tea may help restore overall immunity and protect people from the ubiquitous, toxic environmental chemicals.

References

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2. Kisby GE, Muniz JF, Scherer J, et al. Oxidative stress and DNA damage in agricultural workers. J Agromedicine. 2009;14(2):206-14.

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6. Nnodu U, Whalen MM. Pentachlorophenol decreases ATP levels in human natural killer cells. J Appl Toxicol. 2008 Nov;28(8):1016-20.

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11. Lee DH, Steffes M, Jacobs DR. Positive associations of serum concentration of polychlorinated biphenyls or organochlorine pesticides with self-reported arthritis, especially rheumatoid type, in women. Environ Health Perspect. 2007 Jun;115(6):883-8.

12. Yuminamochi E, Koike T, Takeda K, et al. Interleukin-12- and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill. Immunology. 2007 Jun;121(2):197-206.

13. Masuda Y, Murata Y, Hayashi M, et al. Inhibitory effect of MD-Fraction on tumor metastasis: involvement of NK cell activation and suppression of intercellular adhesion molecule (ICAM)-1 expression in lung vascular endothelial cells. Biol Pharm Bull. 2008 Jun;31(6):1104-8.

14. Gao Y, Zhou S, Jiang W, et al. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol Invest. 2003 Aug;32(3):201-15.

15. Tsukagoshi S, Hashimoto Y, Fujii G, et al. Krestin (PSK). Cancer Treat Rev. 1984 Jun;11(2):131-55.

16. Yang X, Sit WH, Chan DK, et al. The cell death process of the anticancer agent polysaccharide-peptide (PSP) in human promyelocytic leukemic HL-60 cells. Oncol Rep. 2005 Jun;13(6):1201-10.

17. Zheng R, Jie S, Hanchuan D, et al. Characterization and immunomodulating activities of polysaccharide from Lentinus edodes. Int Immunopharmacol. 2005 May;5(5):811-20.

18. Umemura T, Kai S, Hasegawa R, et al. Prevention of dual promoting effects of pentachlorophenol, an environmental pollutant, on diethylnitrosamine-induced hepato- and cholangiocarcinogenesis in mice by green tea infusion. Carcinogenesis. 2003 Jun;24(6):1105-9.

19. López O, Hernández AF, Rodrigo L, et al. Changes in antioxidant enzymes in humans with long-term exposure to pesticides. Toxicol Lett. 2007 Jul 10;171(3):146-53.

20. Singh M, Sandhir R, Kiran R. Erythrocyte antioxidant enzymes in toxicological evaluation of commonly used organophosphate pesticides. Indian J Exp Biol. 2006 Jul;44(7):580-3.

21. Guilford T. Liposomal Glutathione Crucial to Health and Longevity. Vitamin Research News. Available at www.vrp.com.