Infectious disease is the major cause of morbidity and mortality in developing countries, particularly in children. Increasing evidence suggests that protein-calorie malnutrition is the underlying reason for the increased susceptibility to infections observed in these areas. Moreover, certain infectious diseases also cause malnutrition, which can result in a vicious cycle. Malnutrition and bacterial gastrointestinal and respiratory infections represent a serious public health problem. The increased incidence and severity of infections in malnourished children is largely due to the deterioration of immune function; limited production and/or diminished functional capacity of all cellular components of the immune system have been reported in malnutrition. In this review, we analyze the cyclical relationship between malnutrition, immune response dysfunction, increased susceptibility to infectious disease, and metabolic responses that further alter nutritional status. The consequences of malnutrition are diverse and included: increased susceptibility to infection, impaired child development, increased mortality rate and individuals who come to function in suboptimal ways.

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).

Protein-energy malnutrition is the primary cause of immune deficiency in children across the world. It has been related to changes in peripheral T-lymphocyte subsets. The aim of the present study was to evaluate the effects of infection and malnutrition on the proportion of peripheral-lymphocyte subsets in well-nourished non-bacterium-infected (WN), well-nourished bacterium-infected (WNI), and malnourished bacterium-infected (MNI) children by flow cytometry. A prospectively monitored cohort of 15 MNI, 12 WNI, and 17 WN children was studied. All the children were 3 years old or younger and had only bacterial infections. Results showed a significant decrease in the proportion of T CD3 ؉ (P < 0.05 for relative and P < 0.03 for absolute values), CD4 ؉ (P < 0.01 for relative and absolute values), and CD8 ؉ (P < 0.05 for relative values) lymphocyte subsets in WNI children compared to the results seen with WN children. Additionally, B lymphocytes in MNI children showed significant lower values (CD20 ؉ P < 0.02 for relative and P < 0.05 for absolute values) in relation to the results seen with WNI children. These results suggest that the decreased proportions of T-lymphocyte subsets observed in WNI children were associated with infection diseases and that the incapacity to increase the proportion of B lymphocyte was associated with malnutrition. This low proportion of B lymphocytes may be associated with the mechanisms involved in the immunodeficiency of malnourished children.Protein-energy malnutrition is a public health problem in developing countries. Around the world, each year 12 million children under 5 years old die due to the relationship between malnutrition and infectious diseases. Even if malnutrition is very extensive in developing countries, it is rarely considered one of the main mortality causes. However, recent studies indicated that malnutrition in developing countries is an associated death cause in the deaths of more than 50% of children (34). In community studies, a clear relationship between weight decrease and increase of mortality risk has been observed. Also, a solid and systematic relationship between malnutrition and a higher risk of respiratory and diarrhea infections have been detected (27). Several authors have pointed out that malnutrition is the primary cause of immunodeficiency in the world (8,12,32), and it has been related to changes in cellular immunity (8, 29) and changes in peripheral-lymphocyte subsets (mainly CD3 ϩ , CD4 ϩ , and CD8 ϩ ). Nevertheless, results of studies investigating this topic are controversial. In some studies an increase of lymphocyte proportion has been observed; meanwhile, other studies show a decrease in lymphocyte proportions (4,7,10). In a previous study Nájera et al. found no changes in lymphocyte T subsets when malnourished and well-nourished children with bacterial infections were compared (18). These controversial results may be associated with several factors, such as the methods used, the type and degree of malnutrition, and the infection type. For th...

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SummaryMalnutrition continues to be a major public health problem throughout the developing world. Nutritional deficiencies may be the most common cause of secondary immunodeficiency states in humans. It has been suggested that nutritional imbalances can induce apoptosis in a variety of cell types. The purpose of this study was to examine the effect of severe malnutrition on cell subsets and the frequency of spontaneous and/or dexamethasone-induced cell death in vivo in the thymus and spleen from severely malnourished, lactating rats. Apoptosis frequency was estimated by flow cytometry using annexin-V and terminal transferase-mediated dUTP nick-end labelling assay assays. The results obtained in the present study indicate that malnutrition is associated with a significant increase of spontaneously apoptotic cells in the thymus (9·8-fold) and spleen (2·4-fold). Increase in apoptosis was associated largely with CD4 + CD8 + double-positive thymocytes. Unexpectedly, similar frequencies of spontaneous apoptosis of these cells were found in both wellnourished and malnourished rats. In contrast, consistent increases in the apoptosis of CD4 -CD8 -double-negative thymocytes were observed in malnourished rats. In addition, single-positive CD8+ and single-positive CD4 + thymocytes had higher frequencies of apoptosis in malnourished rats. The frequency of total dexamethasone-induced apoptosis was found to be similar in both groups of animals. Nevertheless, in malnourished dexamethasonetreated animals, the percentage of apoptotic double-negative thymocytes was significantly higher than in well-nourished animals, while the rate of apoptosis was lower among double-positive cells. In general, the thymus appears more sensitive to the effects of malnutrition and dexamethasone than the spleen. Furthermore, double-negative thymocytes appear to be the most affected.Keywords: apoptosis, cell death, lymphoid atrophy, malnourished, spleen, thymus

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SummaryMalnutrition compromises immune function, resulting in reduced resistance to infection. Recent animal and human studies have suggested that leptin is capable of modulating the immune response and that its levels, which are regulated by nutritional status, fall rapidly during starvation. Leptin deficiency is associated with impaired cell-mediated immunity, an increased incidence of infectious disease and an associated increase in mortality. The purpose of this study was to examine the effect of leptin on activation and cytokine production in peripheral blood T cells from malnourished children.

SUMMARYThe aim of this study was to determine if the distribution in vivo of CD4 1 CD45RA 1 /CD45RO 2 (naive), CD4 1 CD45RA 1 /CD45RO 1 (Ddull) and CD4 1 CD45RO 1 (memory) lymphocytes differs in malnourished infected and well-nourished infected children. The expression of CD45RA (naive) and CD45RO (memory) antigens on CD4 1 lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 15 malnourished infected, 12 well-nourished infected and 10 well-nourished uninfected children. Malnourished infected children showed higher fractions of Ddull cells (11´4^0´7%) and lower fractions of memory cells (20´3^1´7%) than the well-nourished infected group (8´8^0´8 and 28´1^1´8%, respectively). Well-nourished infected children showed increased percentages of memory cells, an expected response to infection. Impairment of the transition switch to the CD45 isoforms in malnourished children may explain these findings, and may be one of the mechanisms involved in immunodeficiency in these children.