Malnutrition in children is associated with an increased risk of infection and death. Multiple abnormalities in the immune response, including cytokine production, in protein energy-malnourished children have been described and could account for the increased severity and frequency of infections. In this study, we used flow cytometry to investigate the effects of malnutrition on the production of cytokines ؉ and CD8 ؉ cells to produce IL-2, IFN-␥, IL-4, and IL-10 in response to stimulus. We concluded that both cytokine production and activation capacity were impaired in malnourished children. This functional impairment may be involved in the failure to develop a specific immune response and the predisposition to infection in these children.Malnutrition remains one of the most common causes of morbidity and mortality among children throughout the world (1). It is estimated that, in developing countries, more than one-quarter of all children younger than 5 years of age are malnourished (37). Malnutrition has been identified as an important risk factor for predisposition to infections leading to death (36). The strong association between malnutrition and infections has been established through epidemiologic studies conducted in several different countries. The severity of malnutrition determines the risk of death and/or severity of infections (17).Multiple abnormalities in the immune response, including T-cell number, ratio of T-cell subsets, NK cell activity, and cytokine production, have been described in connection with protein energy malnutrition. Nevertheless, results of studies investigating these topics are controversial (13,23,29). Several studies on the effects of malnutrition at the immunological level have been carried out with humans and experimental animals. These studies indicate that malnutrition decreases T-cell function, cytokine production, and the ability of lymphocytes to respond appropriately to cytokines (8,20,6).

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Malnutrition, which is widespread in developing countries, may be particularly devastating during childhood, when tissue development is occurring and nutrient requirements are great. Since protein-energy malnutrition potentially involves many cellular alterations, we have evaluated gene expression changes in lymphocytes from malnourished children using differential hybridization cloning. A cDNA library was generated from well-nourished children and differential screenings were performed with cDNAs obtained from well-nourished and malnourished children who presented with bacterial gastrointestinal infections. Differential expression was detected for genes involved in cell development and differentiation, and for genes involved in lymphocyte and mitochondrial functions. The genes detected in the present study suggest mechanisms for the changes in cell growth and immune function that are associated with protein-energy malnutrition. Two down-regulated genes in malnourished children may represent mechanisms of protection against immunosuppression. This finding clearly merits further investigation.

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