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AIM: In the present study, we examine the effects of copper oxide nanoparticles (CuNP) on macrophage immune response and the signaling pathways involved. MATERIALS & METHODS: A peritonitis model was used to determine in vivo immune cells recruitment, while primary macrophages were used as an in vitro model for the cellular and molecular analysis. RESULTS: In vivo, CuNP induce significant macrophages recruitment to the site of injection. In vitro, in LPS-stimulated primary macrophages, the co-treatment with CuNP inhibited the production of NO in a dose-dependent manner. The mechanism underlying NO and proinflammatory cytokines inhibition was associated with an increased arginase activity. Macrophage stimulation with CuNP did not provoke any cytokine secretion; however, arginase inhibition promoted TNFα and MIP-1ß production. In addition, CuNP induced the expression of COX-2 and the production of PGE2 through arginase activation. CONCLUSION: Our results demonstrate that CuNP activate arginase and suppress macrophage innate immune response.

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OBJETIVO: Esclarecer as repercussões da deficiência de cobre, zinco e magnésio sobre o sistema imune de crianças desnutridas graves. FONTES DE DADOS: Foi realizada revisão bibliográfica mediante consulta às bases de dados Pubmed Medline, Lilacs e SciELO, selecionando-se publicações científicas recentes, da última década, e representativas do tema por meio dos descritores: desnutrição infantil, cobre, zinco, magnésio e sistema imune. SÍNTESE DE DADOS: Os micronutrientes são compostos orgânicos essenciais. Além de sua função regulatória, atuam de maneira decisiva na modulação da resposta imune. Sua deficiência pode ocorrer devido à ingestão inadequada ou associada a doenças específicas. Quando associada à desnutrição, a multideficiência de minerais pode acarretar disfunções imunológicas e aumento na suscetibilidade a infecções, afetando gravemente a eficácia de intervenções terapêuticas. Cobre, zinco e magnésio atuam como cofatores de enzimas responsáveis tanto por diversas atividades metabólicas como na resposta imune inata e adquirida, além do papel importante na maturação dos tecidos e células linfoides. Sua deficiência acarreta neutropenia e linfopenia, comprometendo a imunocompetência. CONCLUSÕES: As alterações ocasionadas pelos déficits séricos dos minerais cobre, zinco e magnésio comprometem o funcionamento do sistema imune, levando à imunossupressão. A reposição desses elementos no manejo da desnutrição grave, como preconizada pela Organização Mundial da Saúde, é essencial, uma vez que tais alterações podem ser reversíveis.

OBJECTIVE: To report the effects of the deficiency of copper, zinc and magnesium on the immune system of severely malnourished children. DATA SOURCE: A literature review was performed by consulting the databases Pubmed Medline, Lilacs and SciELO, using the descriptors: child malnutrition, copper, zinc, magnesium and immune system. Representative studies published during the last decade were chosen. DATA SYNTHESIS: Micronutrients are essential organic compounds. Besides their regulatory function, the minerals act on the modulation of the immune response. Their deficiency may be due to inadequate intake or associated with specific diseases. When combined with malnutrition, a multimineral deficiency can cause immune dysfunction and increased susceptibility to infections, altering the effectiveness of therapeutic interventions. Copper, zinc and magnesium act as co-factors of both enzymes responsible for several metabolic activities and associated to the innate and acquired immune response. These minerals also play an important role in the maturation of lymphoid tissues and cells. Their deficiency causes neutropenia and lymphopenia, decreasing the immunocompetence. CONCLUSIONS: Deficits of serum copper, zinc and magnesium affect the function of the immune system, leading to immunosuppression. The replacement of these elements in the management of severe malnutrition, as recommended by the World Health Organization, is essential, since such changes may be reversible.

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Microminerals including copper and iron are essential to immunity and health in human beings. The development of powerful tools in analytical cell biology and molecular genetics has facilitated efforts to identify specific cellular and molecular functions of trace elements in the maturation, activation and functions of host defence mechanisms. Selected recent reports about the role of copper and iron nutrition on immune functions are critically analysed here. Effects of trace element supplementation on infectious morbidity are also reviewed. While micromineral deficiencies, in general, may have widespread effects on nearly all components of immune response, these effects can be reversed by supplementation. However, the conflicting effects of iron deficiency and iron supplementation in vitro on the defensive systems reveals the urgent need for further additional information on the in vivo situation. In the elderly, vaccination against respiratory infections is likely to protect only 30-70% of the population. However, it may be possible to modulate immune function and ultimately reduce the severity of infections through micronutrient supplementation. Thus, microminerals contribute to the maintenance of the balance between immunity and health in humans.

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