21 - An update on the immunotoxic effects of arsenic exposure

Abstract

Endemic arsenic exposure has emerged as a global public health problem affecting millions of people worldwide because of its association with various cancers and numerous other pathological effects. Increasing lines of research indicate that arsenic may adversely affect the immune system, but its specific target for impairing immune function is poorly understood. While inorganic arsenicals such as arsenite and arsenate show strong cytotoxicity to both macrophages and lymphocytes, arsenic trioxide has important antitumor properties. Arsenic can have significant effects on blood leukocytes and many aspects of the immune system, including impaired T-cell activation, altered expression of cytokines such as interleukin (IL)-2, IL-4, IL-5, IL-10, interferon-gamma and tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor, suppression of contact hypersensitivity responses, loss of adhesion, impairment of function, morphologic changes in human macrophages, and the humoral immune response. Chronic early-life exposure to arsenic in drinking water impairs both the humoral and cellular immune responses, which may lead to an increased risk of infections and inflammatory diseases in infancy, childhood, and adulthood. However, prenatal arsenic exposure in pregnant mothers varies greatly across different geographical locations. Arsenic induces overexpression of keratinocyte-derived growth factors, which are likely to have a significant role in arsenic-induced skin hyperkeratoses and cancer. Chronic arsenic exposure from drinking water causes immunotoxicity by interfering with gene expression and regulation. This chapter presents an update on the immunotoxic effects of arsenic on cells of the human immune system.