Иммунологические аспекты воздействия свинца и кадмия на организм

Abstract

Свинець (Pb) і кадмій (Cd) змінюють імунний статус організму, впливають на процеси, що відіграють важливу роль у виникненні запальних реакцій, аутоімунних захворювань і в розвитку раку. Екологічний вплив Pb і Cd збільшує вразливість до хронічних інфекцій, сприяє виникненню хвороб і поглиблює тяжкість їх протікання. В цілому, надані в огляді дослідження наглядно демонструють той факт, що навіть низькі концентрації Pb та Cd мають негативний вплив на імунний гомеостаз в організмі людини, що особливо небезпечно для дітей, і що знаходить підтвердження в дослідах на тваринах; Свинец (Pb) и кадмий (Cd) изменяют иммунный статус организма, влияя на процессы, играющие важную роль в возникновении воспалительных реакций, аутоиммунных заболеваний и в развитии рака. Экологическое воздействие Pb и Cd увеличивает восприимчивость к хроническим инфекциям, способствуют возникновению болезней, усугубляет тяжесть их протекания. В целом, приведенные в данном обзоре исследования, наглядно демонстрируют тот факт, что даже низкие концентрации Pb и Cd оказывают негативное воздействие на иммунный гомеостаз в организме человека, что особенно опасно для детей и что находит подтверждение в экспериментах на животных; Lead (plumbum) (Pb) and cadmium (Cd) change the parameters of the immune system, leading to a deterioration of the innate and adaptive immunity, causing the decrease in the body’s resistance to autoimmune disease, to infections and allergies. Immunomodulatory activity of Cd and Pb was proved in model systems in vivo and in vitro. The environmental impact of Pb and Cd increases the likelihood of exacerbation of chronic infections, contributes to the emergence of new diseases, aggravates their course. Oxidative stress induced by Cd increases the replication of influenza virus, increases the severity of symptoms and mortality when exposed to sublethal doses of viral infections. HIV-infected individuals contain higher blood levels of Cd. The content of Pb in the blood correlates with the herpes simplex virus type 2. Pb and Cd, in the lesion of the liver with Hepatitis B virus (HBV), enhance viral activity, Cd maintenance of homeostasis is crucial for the survival of Helicobacter pylori in the gastric environment and stimulates the progression of hepatocellular tumors in HBV-infected mice. Pb causes deregulation of production of proinflammatory cytokines TNF-α, IL-1α, IL-6 in macrophages, reduces the phagocytosis and chemotaxis, adversely affects the production of nitric oxide (NO) and metabolism of eicosanoids, causes production of IFN-γ and IL-2 in Th1 lymphocytes. Cd induces synthesis of anti-inflammatory cytokines IL-4 and IL-10 in Th2 lymphocytes. The immune system is very sensitive to the toxic effects of Pb, which affects the immune homeostasis in the human body, being extremely dangerous to children. Impact of Pb reduces the content of natural killer cells (NK), which are the main place of Pb influence on lymphocytes. By the example of Pb impact on lymphocytes, it was shown that heavy metals interact with the immune system in the antigen-nonspecific manner. Unlike with antigen activation on lymphocytes through the receptors, Pb causes their proliferation through signaling pathways related to the metabolism of Ca2+, aggravates the course of the nervous system diseases by enhancing the immunogenicity of neuronal proteins, as exemplified by myelin (MBP) and glial fibrillary acidic protein (GFAP). Immunostimulation, including induction of autoantibodies is the primary immunotoxic effect of Cd, which is related to activation of the polyclonal B-cells, this cause growing trend of autoimmune diseases in the industrialized countries. Even very low levels of Cd exposure during pregnancy lead to long-term harmful effects on the immune system of the offspring, and these effects in some or other degree are associated with the gender. The gastrointestinal tract is one of the main targets of Cd, its oral consumption leads to mucosal damage and inflammation, which is reflected in the increase in the content of pro-inflammatory cytokines TNF-α, IL-1β, IFN-γ and IL-17. Cd is able to influence the production of cytokines through activation of the transcription nuclear kV (NF-kV) factor, which clearly plays a decisive role in the development of inflammatory processes. The thymus is a target organ for Cd. After its action phenotype and rate of lymphocyte proliferatione changes, oxidative stress and apoptosis in T-, B-lymphocytes and macrophages develops. However, Cd impact can cause weight reduction or atrophy of the thymus, as indicated in animal experiments. A protective role of selenium (Se) in hematological and immunosuppressive disorders caused by Cd is widely investigated. Se causes a protective effect in the induced Cd NO-mediated apoptosis in cells of immune organs, reducing their death. Overall, the results of the studies presented in this review clearly show that Pb and Cd in a large extent modulate immune system function.