Mechanistic Overview of Immune Modulatory Effects of Environmental Toxicants (original) (raw)
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The immune system in higher organisms is under integrated control and has the capacity to rapidly respond to the environment. Recently, there has been a significant increase in the prevalence of allergic diseases. Environmental factors likely play a major role in the explosion of allergy. Although the "hygiene hypothesis" may explain the increase in allergic diseases which are prone to T helper 2 (Th2) immune responses, recent findings highlight the possible involvement of environmental xenobiotic chemicals which can modulate normal immune function. Interestingly, several reports suggest that the prevalence of systemic lupus erythematosus, a Th2-type autoimmune disease, is also increasing, although the development of high-sensitivity immunological tests may be a possible cause. The increased prevalence of autoimmune disease in women, the sexual dimorphism of the immune response, and the immunomodulatory effects of sex steroids, have focused attention on the role of chemicals which influence sex steroids in the development of immune diseases. Moreover, recent reports indicate that some environmental chemicals can work on nuclear hormone receptors, other than sex hormone receptors, and modulate immune reactions. This review focuses on the impact of environmental chemicals on immune system function and pathogenesis of immune diseases, including allergy and autoimmune diseases.
Effects of Persistent Organic Pollutants on the Immune System: The Case of Dioxins
2004
Persistent organic pollutants can be traced in air, water, soil and biota in industrialized and non industrialized regions. Although the production of these chemicals has been banned since 1980's when their toxicity was proven, their use, trade and disposal as well as persistence due to previous use, continues to contaminate the environment and threaten human health. Recent studies on the immunological consequences of dioxin contamination and exposure indicate that these compounds and specifically 2, 3, 7, 8Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor on lymphocytes. This activation results in an array of effects on T, B and APC cells, biological mediators of the immune response and thereby results in suppression or remodelling of the immune response. This review attempts to shed light on the recent research developments in this field and to provide insight into the vast and long term health consequences of persistent organic pollutants.
Regulatory Toxicology and Pharmacology, 2014
35 opinions or conclusions contained therein do not necessarily represent the statements, opinions or 36 conclusions of NIEHS, NIH or the United States government. 37 38 This report has been reviewed by the Environmental Protection Agency"s Office of Research and 39 Development and Office of Pesticides Programs, and approved for publication. Approval does not signify 40 that the contents necessarily reflect the views and policies of the Agency nor does mention of trade 41 names or commercial products constitute endorsement or recommendation for use. 42 43 44 2 ABSTRACT (Word count = 199)
Carcinogenesis, 2015
An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides...
Toxicology, 2000
It is now well known that natural (17b-estradiol) and synthetic (e.g. diethylstilbestrol) estrogens not only affect the reproductive system, but also markedly influence the immune system. Recently, a new class of estrogens that is abundant in the environment (in industrial chemicals, pesticides, and surfactants) has been recognized. Some of these estrogenic chemicals (which are a large subgroup of endocrine disrupters) have also been shown to influence the immune system. This review assimilates growing evidence in wildlife, laboratory animals and to a limited extent in humans, which suggests that environmental chemicals may also affect the immune system. Further studies are needed to ascertain the immunological consequences of exposure to environmental estrogens, especially in humans. At the present time, it is not known whether the human immune system responds to a low dose of environmental estrogens or if environmental estrogens influence certain subsets of human populations, rather than the general population. Conceivably, an alteration of the immune system by environmental estrogens could affect the individuals' ability to mount well-regulated immune responses to microbial and vaccine antigens, allergens, self and tumor antigens. Possible changes in the immune system must be investigated routinely in toxicity studies. A comprehensive mechanistic understanding of potential immunomodulatory chemicals is needed. In this regard, relevant laboratory animals may be especially useful in identifying susceptible periods of life, whether both genders are equally affected, in analysis of changes in target lymphoid organs, and to determine the immunological effects of mixtures of chemicals.
Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests
International Journal of Environmental Research and Public Health
With the outbreak of COVID-19, increasingly more attention has been paid to the effects of environmental factors on the immune system of organisms, because environmental pollutants may act in synergy with viruses by affecting the immunity of organisms. The immune system is a developing defense system formed by all metazoans in the course of struggling with various internal and external factors, whose damage may lead to increased susceptibility to pathogens and diseases. Due to a greater vulnerability of the immune system, immunotoxicity has the potential to be the early event of other toxic effects, and should be incorporated into environmental risk assessment. However, compared with other toxicity endpoints, e.g., genotoxicity, endocrine toxicity, or developmental toxicity, there are many challenges for the immunotoxicity test of environmental pollutants; this is due to the lack of detailed mechanisms of action and reliable assay methods. In addition, with the strong appeal for ani...
Approaches to risk assessment of immunotoxic effects of chemicals☆
Toxicology, 2001
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