Impact of Heat-Killed Lactobacillus casei Strain IMAU60214 on the Immune Function of Macrophages in Malnourished Children.

Malnutrition is commonly associated with immunological deregulation, increasing the risk of infectious illness and death. The objective of this work was to determine the in vitro effects of heat-killed Lactobacillus casei IMAU60214 on monocyte-derived macrophages (MDMs) from well-nourished healthy children, well-nourished infected children and malnourished infected children, which was evaluated by an oxygen-dependent microbicidal mechanism assay of luminol-increase chemiluminescence and the secretion of tumor necrosis factor (TNF-α), interleukin (IL-1ß), IL-6 and IL-10, as well as phagocytosis using zymosan and as its antibacterial activity against Salmonella typhimurium, Escherichia coli and Staphylococcus aureus. We found that reactive oxygen species (ROS), secretion cytokines (TNFα, IL-1ß, IL-6 and IL-10 levels), phagocytosis and bactericidal capacity increased in all groups after pre-treatment with heat-killed L. casei IMAU60214 at a ratio of 500:1 (bacteria:MDM) over 24 h compared with MDM cells without pre-treatment. The results could indicate that heat-killed L. casei IMAU60214 is a potential candidate for regulating the immune function of macrophages.

Perinatal malnutrition programs sustained alterations in nitric oxide released by activated macrophages in response to fluoxetine in adult rats.

OBJECTIVE: Nutritional restriction during lactation has long-term consequences on the functioning of neuroimmune systems. Receptors and transporter serotonin (5-HT) are present in macrophages and may influence their role. This study evaluated nitric oxide release by alveolar macrophages (AMs) in adult control rats and rats malnourished during lactation in response to different fluoxetine (FLX) concentrations and 5-HT(1A) and 5-HT(1B) agonists at different times. METHODS: Male Wistar rats were distributed into two groups according to maternal diet during lactation: a control group of 12 rats whose dams had received a 23% protein diet and a malnourished group of 12 rats whose dams had received an 8% protein diet. After weaning, all rats received a 23% protein diet. On the 90th day after birth, nitric oxide (NO) release kinetics was measured in supernatants of AMs cultured with FLX. The NO release following the adjunction of serotoninergic agonists was also quantified. RESULTS: The malnourished rats weighed less at weaning (control rats = 15.3 +/- 0.4 g, malnourished rats = 11.8 +/- 0.4 g); this difference persisted until 90 days of life (control rats = 355.4 +/- 8.6 g; malnourished rats = 267.8 +/- 7.9 g). In the presence of 10(-6)M FLX, NO release by AMs in control rats was lower. The addition of agonists did not interfere with NO release by AMs in control rats. NO release by AMs from malnourished rats was modified neither by FLX nor by agonists. As a consequence of malnutrition, there were lower numbers of cells and AMs in the bronchoalveolar lavage fluid, and cell viability and NO release by AMs were impaired. CONCLUSIONS: Nutritional manipulation in the perinatal period seems to interfere with the functional programming of macrophages; it also seems to affect their serotoninergic regulation through adulthood.

Neonatal programming of neuroimmunomodulation--role of adipocytokines and neuropeptides.

Programming is an epigenetic phenomenon by which nutrition, environment and stress acting in a critical period earlier in life change the organism's development. This process was evolutionarily selected as an adaptive tool for the survival of organisms living in nutritionally deficient areas and submitted to stressful conditions. Thus, perinatal malnutrition turns on different genes that provide the organism with a thrifty phenotype. In conditions of abundant supply of nutrients, those programmed organisms can be at risk of developing metabolic diseases (obesity, dyslipidemia, diabetes and hypertension). How nutrition or neonatal stress can program the immune system is less well known. Here, we discuss some of the hormonal and metabolic changes that occur in mothers and neonates and how those factors can imprint hormonal or metabolic changes that program neuroimmunomodulatory effects. Some of these changes involve thyroid hormones, leptin, insulin, glucocorticoids and prolactin as potential imprinting factors. Most of them can be transferred through the milk and may change with malnutrition or stress. We discuss the programming effects of these hormones upon body weight, body composition, insulin action, thyroid, adrenal and immune and inflammatory responses, with special emphasis on leptin, a cytokine that seems to play a central role in these events.

Stress/aggressiveness-induced immune changes are altered in adult rats submitted to neonatal malnutrition.

BACKGROUND/AIMS: Neonatal malnutrition induces metabolic and endocrine changes that have beneficial effects on the neonatal in the short term but, in the longer term, these alterations lead to maladaptations. We investigated the effect of neonatal malnutrition on immune responses in adult rats submitted or not to an aggressiveness test. METHODS: Male Wistar rats were distributed to one of two groups according to their mothers' diet during lactation: the well-nourished group (group C, n = 42, receiving 23% of protein) and the malnourished group (group MN, n = 42, receiving 8% of protein). After weaning, all rats received normoproteic diet. Ninety days after birth, each group was subdivided into three subgroups: control rats (n = 14, respectively), aggressive rats (n = 14, respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma corticosterone concentration was measured after FS sessions. Leukocyte counts and humoral immunity were evaluated. RESULTS: In neonatal malnourished animals, FS-induced stress reduced plasma corticosterone concentration. Intraspecific aggressiveness induced alterations in leukocyte counts and antibody titers 7 and 15 days after immunization. Neonatal malnourished animals showed no changes in the immune parameters evaluated. CONCLUSIONS: Expression of intraspecific aggressiveness activates the immune system. Neonatal malnutrition seems to have a long-lasting effect on components of both neuroendocrine and immune functions.

Current status of digestive intolerance to food protein.

Digestive intolerance to food proteins may occur in childhood as a result of a wide range of etiologic and pathophysiologic mechanisms. Cow milk protein intolerance is the most common form of food intolerance in children. Food allergy and food intolerance may be confused because both produce similar symptoms, especially in young children with clinical manifestations of food allergy localized to the gastrointestinal tract. On the other hand, food-sensitive enteropathy may be defined as the clinical food-related syndromes associated with an abnormal small intestinal mucosa. Although several foods have been reported to damage the small intestinal mucosa in infancy (soy, rice, fish, chicken meat, egg), cow milk-sensitive enteropathy is the most common cause. Whatever the mechanisms, digestive intolerance to food proteins with or without enteropathy is primarily a temporary condition of infancy, in contrast to most forms of food allergy. In children with these disorders, symptoms usually resolve by 1 to 3 years of age. The variation in prevalence rates of this disorder in different countries can be explained by different diagnostic criteria. The classic food-sensitive enteropathy syndromes with chronic diarrhea and failure to thrive in infancy have become rarer in some European countries, including Spain. Some risk factors for the development of these conditions appear to be early exposure to cow milk feedings, acute infectious diarrhea, and malnutrition. Breast-feeding appears to be at least partially protective.

Allergenicity and nutritional adequacy of soy protein formulas.

Soy protein formulas are used for different conditions, including cow milk protein allergy, lactose and galactose intolerance, and severe gastroenteritis. Feeding soy protein formulas to normal term infants is associated with normal growth, normal protein nutritional status, and normal bone mineralization. Recent studies of infants fed soy protein formulas exclusively during the first months of life revealed no immunologic abnormality; however, the use of such formulas for management of cow milk protein allergy and for prevention of atopy is controversial. Although in the past decade many studies have stressed soy allergenicity, soy allergenicity has been confirmed by the challenge test in only a few studies. In this article we review the studies dealing with the allergenicity of soy protein formulas. We also present our own data on their use in the prevention and management of cow milk protein allergy.

[Quantification of number and function of mononuclear cells. Fc gamma receptors in children with protein-calorie malnutrition (PCM)]. / Cuantificación del número y la función de las células mononucleares. RFc gamma de niños con desnutrición proteico-calórica (DPC).

Several kind of cells T membrane receptors have been recognized, between them immunoglobulins heavy chains receptors mu and gamma, they act in the antigen recognition, they are subpopulations-cells T surface-matched too. In the malnutrition protein-calorie (MPC) immunologic alterations were observed, in both cellular immune and humoral immune, for example: The immunoglobulins are increased and cellular response towards antigens is decreased. This failure can be due to dysfunction in the lymphocyte T-subpopulation. So we research if there are different number, percent and function of lymphocytes T subpopulations between children with MPC and health infant. We observed an increment of lymphocytes T gamma in number and percent in children with MPC compared with health infant (p < 0.05) However, the lymphocytes T and subpopulation gamma response to phytohemagglutinin was bad. These findings are concordant with the literature about increased in lymphocyte T gamma of children with MPC. Additionally we observed a dysfunction in this subpopulation.

Response of mildly to moderately malnourished children to measles vaccination

Nutritional aspects of measles vaccination were examined in 51 Trinidadian children from one to three years of age with no prior history of measles. The subjects were divided into two weight-for-length groups derived from the Havard Standards and included 22 children with a weight-for-length of 90 percent or greater and 29 children with a weight-for-length of less than 90 percent. There were no significant differences in the two groups in general immune function, as assessed by white blood cell counts, immunoglobulin and C3 levels, nor in immune response, as assessed by measles antibody titres and direct migration inhibition of leukocytes to measles antigen following vaccination. All of the subjects seroconverted following vaccination, with titres of 1:40 or above. There were no significant changes in nutritional status in either group following vaccination, other than a small but significant rise in total serum protein levels in the normal group. (AU)

Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses.

To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses.

Development of impaired cell-mediated immunity in mild and moderate malnutrition.

The development of moderate malnutrition and cell-mediated immune function was studied in 71 Colombian infants from birth through 2 yr of age. Based upon weight-for-age criteria 31 remained normal, 33 were classified as grade I, and seven were grade II malnourished at the end of their 2nd yr of life. Delayed hypersensitivity reactions to purified protein derivative were significantly reduced in all malnourished children 8 wk after Bacille Calmette-Guerin vaccination at birth, and also at 2 yr in the Grade II group. Nearly half of the latter group could not be sensitized to dinitrochlorobenzene at 2 yr of age. A 50% reduction in the blastogenic response of peripheral blood lymphocytes to phytohemagglutinin in vitro was detected in grade II children. Both mildly and moderately malnourished infants exhibited a significant reduction in tonsil size at 2 yr of age. These results indicate that a majority of newborns in this poor, urban setting will develop measurable malnutrition associated with impaired cell-mediated immune function before their 2nd birthday.

PMN cell phagocytic function in malnourished patients with zinc uptake.

Zinc effects on phagocytic activity depend upon its serum concentration. According to certain experimental findings, a decrease in zinc serum concentration is parallel to a deficiency in host defense mechanisms and thus we were interested in studying the effect of zinc sulphate in the phagocytic function of polymorphonuclear cells of 15 zinc deficient patients with III degree malnourishment. In all patients, zinc serum determinations were made before and after zinc intake and chemotaxis, phagocytosis and NBT reduction tests were made at 7, 14 and 30 days. Results are compared with an eight patient group with similar clinical and nutritional characteristics observing an improvement in PMN cell phagocytic activity in patients with zinc uptake (p < 0.001). No differences were observed in a chemotaxic phagocytosis and NBT reduction tests in regard to the time during which patients did not receive zinc uptake.

Exploración del sistema inmune en lactantes desnutridos / Examination of the immune system in infants with malnutrition

Se investigó la reactividad inmunitaria en un grupo de niños en estados variados de desnutrición mediante la exploración del sistema inmune-humoral y celular, con la finalidad de comprobar si una hiporreactividad inmunitaria participa del proceso. La experiencia se desarrollo sobre 18 desnutridos (con pérdida de peso comprendida entre el 30 y el 57 %) y un grupo control de 16 eutróficos cuyas edades oscilaron entre 4 meses y un año. En la exploración del sistema inmune-humoral se observó en los desnutridos un aumente de las glubulinas totales, de las gammaglobulinas y de las tres inmunoglobulinas G, A y M estudiadas. No se ha encontrado hipogammaglobulinemia en ninguno de los casos estudiados. Los valores para Ig G, Ig A e Ig M revelan cifras similares en ambos grupos, con un leve aumento en los desnutridos. No hubo déficit de inmunoglobulinas en los desnutridos. La exploración del sistema timodependiente reveló una disminución de la reactividad retardada infecciosa para la Escherichia coli y la Candida albicans y de la de contacto para el dinitroclorobenzeno. El estudio realizado parecería indicar en déficit inmunológico del sistema inmune-celular y un estado normal o quizás algo exaltado del sistema inmune-humoral.