Supplementation of Ocean-Based Advance Protein Powder (APP) for Restoration of Body Growth, Bone Development and Immune Functions in Protein Malnourished Mice: Implications for Preventing Child Malnutrition.

Child malnutrition is a global public health challenge. A protein malnutrition (PM) model in young mice was established in this study. The efficacy of an ocean-based protein (APP) extracted from by-catch fish as compared to casein and soy on restoring body weight, bone growth, and immunity of PM mice was evaluated. Results show that supplementation of APP increases body weight, lean muscle mass, bone area, mineral content and density. APP supplementation increases spleen, thymus weight, and interlukin-6 production. In conclusion, APP is an alternative source of protein to effectively restore body weight, bone growth and immune function of PM mice.

Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner.

Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection.

Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model.

BACKGROUND: Low efficacy of rotavirus (RV) vaccines in developing African and Asian countries, where malnutrition is prevalent, remains a major concern and a challenge for global health. METHODS: To understand the effects of protein malnutrition on RV vaccine efficacy, we elucidated the innate, T cell and cytokine immune responses to attenuated human RV (AttHRV) vaccine and virulent human RV (VirHRV) challenge in germ-free (GF) pigs or human infant fecal microbiota (HIFM) transplanted gnotobiotic (Gn) pigs fed protein-deficient or -sufficient bovine milk diets. We also analyzed serum levels of tryptophan (TRP), a predictor of malnutrition, and kynurenine (KYN). RESULTS: Protein-deficient pigs vaccinated with oral AttHRV vaccine had lower protection rates against diarrhea post-VirHRV challenge and significantly increased fecal virus shedding titers (HIFM transplanted but not GF pigs) compared with their protein-sufficient counterparts. Reduced vaccine efficacy in protein-deficient pigs coincided with altered serum IFN-α, TNF-α, IL-12 and IFN-γ responses to oral AttHRV vaccine and the suppression of multiple innate immune parameters and HRV-specific IFN-γ producing T cells post-challenge. In protein-deficient HIFM transplanted pigs, decreased serum KYN, but not TRP levels were observed throughout the experiment, suggesting an association between the altered TRP metabolism and immune responses. CONCLUSION: Collectively, our findings confirm the negative effects of protein deficiency, which were exacerbated in the HIFM transplanted pigs, on innate, T cell and cytokine immune responses to HRV and on vaccine efficacy, as well as on TRP-KYN metabolism.

Protein deficiency lowers resistance of Mormon crickets to the pathogenic fungus Beauveria bassiana.

Little is known about the effects of dietary macronutrients on the capacity of insects to ward off a fungal pathogen. Here we tested the hypothesis that Mormon crickets fed restricted protein diets have lower enzymatic assays of generalized immunity, slower rates of encapsulation of foreign bodies, and greater mortality from infection by Beauveria bassiana, a fungal pathogen. Beginning in the last nymphal instar, Mormon crickets were fed a high, intermediate, or low protein diet with correspondingly low, intermediate, or high carbohydrate proportions. After they eclosed to adult, we drew hemolymph, topically applied B. bassiana, maintained them on diet treatments, and measured mortality for 21 days. Mormon crickets fed high protein diets had higher prophenoloxidase titers, greater encapsulation response, and higher survivorship to Beauveria fungal infection than those on low protein diets. We replicated the study adding very high and very low protein diets to the treatments. A high protein diet increased phenoloxidase titers, and those fed the very high protein diet had more circulating prophenoloxidase. Mormon crickets fed the very low protein diet were the most susceptible to B. bassiana infection, but the more concentrated phenoloxidase and prophenoloxidase associated with the highest protein diets did not confer the greatest protection from the fungal pathogen as in the first replicate. We conclude that protein-restricted diets caused Mormon crickets to have lower phenoloxidase titers, slower encapsulation of foreign bodies, and greater mortality from B. bassiana infection than those fed high protein diets. These results support the nutrition-based dichotomy of migrating Mormon crickets, protein-deficient ones are more susceptible to pathogenic fungi whereas carbohydrate-deficient ones are more vulnerable to bacterial challenge.

The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells.

Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1ß, IL-6, IL-10, TGF-ß and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1ß, IL-6 and TGF-ß was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs.

Effects of protein malnutrition on tolerance to helminth infection.

Infection tolerance is the ability of a host to limit the health effects of a given parasite load. A few recent studies have demonstrated genetic variation for tolerance, but little is known about how environmental factors affect tolerance. Here, we used the intestinal nematode Heligmosomoides polygyrus in laboratory mice to test for effects of protein malnutrition on tolerance. We performed an experiment where two different mouse strains (CBA and BALB/c) were fed either adequate-protein food or low-protein food, and trickle-infected with different doses of H. polygyrus larvae during four weeks. We found that protein malnutrition decreases tolerance measured as intestinal barrier function, but only in one of the strains (BALB/c); that is, there was a host genotype-by-environment interaction for tolerance. We conclude that nutritional status can affect tolerance and that sensitivity of tolerance to malnutrition may differ between host genotypes.

Curcumin protects against nicotine-induced stress during protein malnutrition in female rat through immunomodulation with cellular amelioration.

Nicotine aggravates many chronic inflammatory disorders in females under the protein-malnourished conditions because women are more susceptible to nicotine-induced diseases due to their low innate immunity. Although curcumin have been found to obliterate the nicotine-induced disorders through its anti-nicotinic activity under the protein-malnourished condition, the exact mechanism of protective action of curcumin is still unclear. Female Wister rats maintained under the normal and protein-restricted diets in two separate groups were injected with the effective dose of nicotine-tartrate (2.5 mg/kg body weight/day, subcutaneously) and supplemented with the effective dose of curcumin (80 mg/kg body weight/day, orally) for 21 days. The morphology of red blood cells (RBCs), molecular docking, lipid profile and activities of antioxidant enzymes in tissues, cytokines profiling (T helper cell type 1; and T helper cell type 2), mRNA and protein expression of cytokines, transcription factors (activator protein 1), regulatory molecule (P(53)), growth factors (Granulocyte-macrophage colony-stimulating factor; Transforming growth factor beta) were determined to establish the mechanism of actions of curcumin against the nicotine-mediated stress in the protein-malnourished rats. This study revealed that curcumin bound to the Histidine 87 residues of haemoglobin with a greater binding affinity and significantly protected the RBCs against nicotine-induced damage. Furthermore, the nicotine-mediated disruption of Th1/Th2 balance through upregulation and downregulation of different factors was effectively restored by curcumin under the protein-malnourished conditions. The study demonstrated that curcumin was a potent protective compound against the nicotine-induced stress and offered a probable biochemical and immunomodulatory mechanism of protective action of curcumin.

[Controversies around diet proteins]. / Kontrowersje wokól bialek diety.

Critical theories regarding proteins of anima origin are still and still popularized, though they are ungrounded from scientific point of view. Predominance of soya proteins over the animal ones in relation to their influence on calcium metabolism, bone break risk or risk of osteoporosis morbidity has not been confirmed in any honest, reliable research experiment. Statement, that sulphur amino acids influence disadvantageously on calcium metabolism of human organism and bone status, is completely groundless, the more so as presence of sulphur amino acids in diet (animal proteins are their best source) is the condition of endogenic synthesis of glutathione, the key antioxidant of the organism, and taurine stimulating brain functioning. Deficiency of proteins in the diet produce weakness of intellectual effectiveness and immune response. There is no doubt that limitation of consumption of animal proteins of standard value is not good for health.

Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.

Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.

Hot water extracts of Chlorella vulgaris improve immune function in protein-deficient weanling mice and immune cells.

The objective of this study was to investigate the effects of hot water extracts of Chlorella vulgaris (CVE) on a deteriorated immune function through utilization of a protein-energy malnutrition (PEM) diet. Unicellular algae, C. vulgaris, were used as biological response modifier. PEM is associated with decreased host immune defense. Male C57BL/6J mice, initially four weeks old, were fed for 8 days with standard diet or a PEM diet. Mice in the PEM diet group were orally administered 0.1 g/kg and 0.15 g/kg of CVE for the following week. Nutritional parameters such as the total protein, albumin, glucose, and interferon γ (IFN-γ) were increased in blood serum of the CVE-treated group compared with the non-treated group. The mononuclear cell numbers from spleen, superficial, and mesenteric lymph node were reduced in mice fed with PEM diet, but numbers from the spleen and superficial lymph node were increased by the CVE (0.1 and 0.15 g/kg) treatment. We also investigated the effect of CVE on the production of cytokines in human T-cell line, MOLT-4 cells, and primary cultured splenocytes. The CVE treatment significantly increased the production of both interleukin (IL)-2 and IL-4 compared with the media control, but did not affect the production of IFN-γ. These results suggest that CVE may be useful in improving the immune function.

Tissue mineral distributions are differentially modified by dietary protein deficiency and a murine nematode infection.

This study was designed to investigate whether mineral concentrations in the spleen, serum, and liver were modified by challenge infection with a gastrointestinal nematode, by infection dose, or by protein deficiency despite adequate dietary intakes of minerals. BALB/c mice fed protein-sufficient (PS, 24%) or protein-deficient (PD, 3%) diets were infected with 100 L3 of Heligmosomoides bakeri, drug-treated, and then re-infected with either 0, 100, or 200 L3. Protein deficiency and infection, but not dose, independently modified tissue mineral distributions. H. bakeri infection lowered serum iron concentrations in both diet groups. Despite this, PD mice had elevated iron and calcium concentrations and Ca/Zn ratio in the spleen as well as Fe/Zn ratio in liver, but they had reduced calcium, zinc, copper, and sulfur concentrations, and Cu/Zn ratio in the liver. Infection reduced calcium and iron concentrations and the Ca/Zn ratio in the spleen. We suggest that tissue mineral distribution is a consequence of Th2 immune and inflammatory responses induced by infection in PS mice and the switch to predominant Th1 inflammation in PD, nematode-infected mice.

Nutrition disorder and immunologic parameters: study of the intestinal villi in growing rats.

OBJECTIVE: The aim of the present work was to study how a diet in which cereals were the only protein source would affect B and T lymphocytes and a cell population positive for thymus-expressed chemokine (TECK) in the intestinal villi of growing rats. METHODS: Wistar rats were fed a 6.5% precooked maize protein diet for 18-20 d (M group). An age-matched control group received stock diet (C group). Body weight (grams) was determined, ponderal growth rate (grams per day per 100 g) was calculated, and intestines were removed and processed by Saint-Marie's technique. Tissue sections were studied by indirect immunofluorescence. CD5(+) T cells and the T-cell subsets TCRalphabeta(+), TCRgammadelta(+), CD4(+), CD8alpha(+), and CD8beta(+) in the lamina propria (LP) and intraepithelium, in addition to immunoglobulin A-positive B cells in the LP were determined (n cells/30 fields were read). In addition, the presence of the TECK(+) cell population was qualitatively assessed. RESULTS: The M versus C group showed statistically significant differences in body weight and ponderal growth rate. The number of immunoglobulin A-positive B cells in the LP and the CD5(+) T cells and CD4(+), CD8alpha(+), CD8beta(+), TCRalphabeta(+), and TCRgammadelta(+) T-cell subpopulations of the M group in the LP and intraepithelium of the gut villi were significantly decreased compared with the C group (P < 0.001). The M group also showed differences in the size and cellularity of the gut villi and in the distribution of TECK. CONCLUSION: The results show that intake of a low concentration of a low-quality dietary protein as the only source of protein produces an important disorder in the mucosal immunity of experimental rats.

Re-feeding rapidly restores protection against Heligmosomoides bakeri (Nematoda) in protein-deficient mice.

This study determined whether the timing of re-feeding of protein-deficient mice restored functional protection against the gastrointestinal nematode, Heligmosomoides bakeri. Balb/c mice were fed a 3% protein-deficient (PD) diet and then transferred to 24% protein-sufficient (PS) diet either on the day of primary infection, 10 days after the primary infection, on the day of challenge infection, or 7 days after the challenge infection. Control mice were fed either the PD or PS diet. Onset of challenge, but not primary, infection caused short-term body weight loss, anorexia and reduced feed efficiency. Weight gain was delayed in mice when re-feeding commenced on the day of challenge infection; alkaline phosphatase (ALP) was also elevated in these mice on day 28 post-challenge. In contrast, other re-feeding groups attained similar body weights to PS mice within 4 days and had similar ALP at day 28. Serum leptin was higher in PD than PS mice and positively associated with food intake. As expected, worm survival was prolonged in mice fed the PD diet. However, egg production and worm burdens were similar in all re-feeding groups to the PS mice, indicating that protein re-feeding during either the primary or challenge infection rapidly restored normal parasite clearance.

Dietary protein deficiency in pregnant mice and offspring.

Previous studies suggest an association between dermal contact hypersensitivity and preterm delivery. We hypothesized that dietary protein deficiency produces cell-mediated immune hypersensitivity in pregnant animals and their offspring akin to those known to produce tissue damage. We compared the effects of feeding a 20% protein diet (controls) to those of feeding a 10% protein (deficient) diet ad libitum to pregnant BALB/c mice. We measured dermal contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) by the increment in ear skin thickness (swelling) 72 h after immunization and parity by the number of viable pups delivered. Dams fed the protein-deficient diet ingested less food, gained less weight and delivered fewer viable pups than the dams fed the control diet. Greater DNFB-stimulated increment in ear skin thickness was found in the protein-deficient mothers and in their offspring than in the control mothers and their offspring. We conclude that dietary protein deficiency limits parity and induces immune hypersensitivity. These findings suggest the potential for dietary protein deficiency to activate a T-cell-mediated branch of the immune response that may put pregnant animals at risk for preterm delivery.

Protein deficiency impairs DNA vaccine-induced antigen-specific T cell but not B cell response in C57BL/6 mice.

DNA vaccination is a simple method to induce antigen (Ag)-specific immunoresponse and has many potential advantages over other vaccines. Although people who need to receive vaccines often suffer undernutrition, there has been no study on a how nutritional status affects the immunoresponse induced by DNA vaccination. The aim of this study was to determine the relationship between protein deficiency and DNA vaccine-induced immunoresponses. C57BL/6 mice were fed a 5% or 20% casein diet for 30 d. The mice were immunized with an ovalubumin (OVA)-expression plasmid by the gene gun-based method three times at 10-d intervals. Body weight and serum albumin concentration in protein-deficient mice were significantly lower than those in mice fed the 20% casein diet (p<0.01, p<0.05). The percentage of OVA-specific CD8+ T cells was significantly decreased in the 5% casein group compared to that in the 20% casein group (p<0.05). Furthermore, CD4+ T cells from mice fed the low-protein diet showed lower interleukin (IL)-2 production than did those from the 20% group. In contrast to the T-cell function, protein deficiency did not affect OVA-specific Ab responses (p>0.05). These results suggest that protein deficiency impairs the induction of Ag-specific T-cell but not B-cell response in DNA-immunized mice. Our observation indicates that, in addition to development of an effective of DNA vaccine, the management of nutritional state is important for the prevention of infectious disease by DNA vaccination.

Elevated bioactivity of the tolerogenic cytokines, interleukin-10 and transforming growth factor-beta, in the blood of acutely malnourished weanling mice.

The main objective of this investigation was to determine the influence of acute deficits of protein and energy on the blood levels of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), physiologically the main anti-inflammatory and tolerogenic cytokines. In four 14-day experiments, male and female C57BL/6J mice, initially 19 days old, consumed a complete purified diet either ad libitum or in restricted daily quantities, or had free access to an isocaloric purified low-protein diet. A zero-time control group (19 days old) was included. In the first two experiments, serum IL-10 levels were assessed by sandwich enzyme-linked immunosorbent assay (ELISA) and bioassay. The mean serum IL-10 bioactivities were higher (P < or = 0.05) in both malnourished groups (low-protein and restricted intake: 15.8 and 12.2 ng/ml, respectively) than in the zero-time and age-matched control groups (6.3 and 7.3 ng/ml, respectively), whereas serum IL-10 immunoactivity was high only in the restricted intake group (e.g., second experiment: 17.0 pg/ml vs. 5.4, 3.7, and 3.1 pg/ml in the zero-time control, age-matched control and low-protein group, respectively). The third and fourth experiments centered on plasma TGF-beta immunoactivity (sandwich ELISA) and bioactivity, respectively. The ELISA revealed a high mean plasma TGF-beta1 level (P < or = 0.05) in the low-protein group only, but TGF-beta bioactivity (beta1 isoform, although 15% beta2 in the restricted intake group) was high in both malnourished groups (8.7 and 9.3 ng/ml in the low-protein and restricted groups, respectively) relative to the age-matched control group (0.5 ng/ml). Thus, metabolically distinct weanling systems mimicking marasmus and incipient kwashiorkor both exhibit a blood cytokine profile that points to a tolerogenic microenvironment within immune response compartments. A model emerges in which malnutrition-associated immune competence, at least in advanced weight loss, centers on cytokine-mediated peripheral tolerance that reduces the risk of catabolically induced autoimmune disease, but this is at the cost of attenuated responsiveness to infectious agents.

Long-term effect of early protein malnutrition on growth curve, hematological parameters and macrophage function of rats.

To evaluate the long-term effect of mild-early maternal protein malnutrition on weight gain, hematological parameters and macrophage function in rats at adult age, we compared rats whose dams were fed diets containing either 9.5% (low protein-LPD) or 23% protein (normal-NPD) for the first 12 d of lactation. At 80 d of age, the functions of spreading, phagocytosis and killing Candida albicans were determined in resident peritoneal macrophages, whereas leukocytes and red blood cells were counted in peripheral blood. The number of resident peritoneal macrophages from LPD was the same as from NPD, but the ability of spreading and phagocytosing opsonised yeast was impaired. Besides, they were not able to block the germ tube formation or kill C. albicans to the same extent as in the control group. The low protein diet produced a significant reduction in the pups' growth and in hematological parameters although no difference was found in leukocyte counts. Taken together the data suggest that protein malnutrition during early lactation induces permanent alterations in macrophage function, body composition and hematological status, which are not restored completely even after a normal protein diet is supplied.

Compartmentalisation between gut and lung mucosae in a model of secondary immunodeficiency: effect of thymomodulin.

UNLABELLED: Compartmentalisation of mucosal immune response seems to be the result mainly of the preferential migration of activated cells back to their inductive sites. The aim of this report was to demonstrate, in a model of secondary immunodeficiency in Wistar rats (severely protein deprived at weaning and refed with casein 20%; group R21), that the oral administration of Thymomodulin (group:R21TmB) has different effects on gut and BALT (Bronchus-associated lymphoid tissue). Tissue sections (5 mu) were studied by immunohistochemistry 1). The oral administration of Thymomodulin restores only in gut Lamina propria (LP) the IgA B and CD4 T cell populations to control levels. The CD8a and CD25 subpopulations do not vary in gut as they return to control levels when refed with 20% casein diet. All the populations mentioned above remained decreased even after receiving Thymomodulin by the oral route. However, the same behaviour was observed for the TCR delta T cells that were decreased and return to normal levels in both mucosae by the effect of the immunomodulator; 2) when studying the iIEL (intestinal intraepithelial lymphocytes) CD8 alpha, CD25 and TCR gamma delta T cells, that were increased in R21, return to control levels in R21TmB. In BALT intraepithelium CD8 alpha and CD25 T cells remained decreased, while only TCR gamma delta T cells (increased in R21) return to control values. CONCLUSIONS: 1) there exists a compartmentalisation between both mucosae, as T CD4+ and IgA B+ cells are restored by TmB only in gut; 2) only those iIEL involved in inflammation (CD8 alpha+/CD25+ and TCR gamma delta+/CD25+) are normalised by means of the Thymomodulin 3) however, in BALT,only TCR gamma delta+ T cells are restored 4) the oral administration of the present immunomodulator may be useful as a therapeutic agent, although the preferential survival in the tissue of initial stimulation is the major factor in the preferential distribution of activated cells.

Oral tolerance to dextrin mediated by specific suppressor T-cells induced in the intestinal intraepithelium and their systemic migration.

Antigens presented to the immune system through the oral route induce antigen specific secretory IgA and systemic unresponsiveness, termed oral tolerance (OT). We studied the induction of OT towards a diet antigen: dextrin (DEX) in rats that underwent protein deprivation and were further re-fed. Peyer's patches (PP), mesenteric lymph nodes (MLN) and spleen (Sp) cells from protein re-fed (R) rats mediated hyporesponsiveness after transfer into naïve recipient rats. Low numbers of MLN T cells transferred hyporesponsiveness while higher numbers transferred an enhancement of the delayed type hypersensitivity (DTH) reaction. MLN T cells were further separated based on their ability to bind Vicia villosa (VV). MLN VV- T cells, mainly CD8+, mediated hyporesponsiveness and MLN VV+ T cells (CD45RC+ CD4- CD8- cells) abrogated the hyporesponsiveness. Moreover, Sp DEX adherent T cells were mainly CD8+. Intestinal intraepithelial lymphocytes (iIELs) mainly CD8alpha+ gamma(delta)-TCR+ cells also inhibited the DTH response to DEX after transfer. The positive DTH response to another carbohydrate (levan) indicates the specificity of the suppression to dextrin. Therefore, our data indicate that after oral administration of DEX, two different populations of T cells were generated: one found only in the MLN that mediated DTH responses and the other one capable of migrating from the intestinal intraepithelium through PP and MLN to the Sp, mediating systemic tolerance.

[Gene expression of Interleukin 1 in vitamin A and proteins deficiency]. / Expresión génica de interleucina 1 en la deficiencia de proteínas y vitamina A.

The influence of low levels of protein and vitamin A on indicators of the immune response was assayed in rats. The levels of protein and vitamin A intake of the Cuban population affected by epidemic neuropathy in 1993 was reproduced in 4 diets: control, protein deficiency (DP), vitamin A deficiency (DA), protein and vitamin A deficiency (DAP). The Peyer's patches evaluated the Interleukin 1 expression gene and was related with corporal weight, food intake, serum protein, vitamin A, immunology indicators and histology evaluation (spleen, thymus and liver). Protein deficiency generated a significant decrease of the expression gene of Interleukin 1. Atrophy signs in lymphoid tissues and morphologic changes in the liver were associated with the dietary protein utilization. Protein and vitamin A deficiency generated significant stimulation of the Interleukin 1 expression gene with increase of the level of the inflammatory state indicators as serum alpha protein, total complement and neutrophils. This stimulation could be generated by a deficient retinol mobilization to tissues. These results support the hypothesis of the function of cytokines as mediators of subclinical symptoms of the immune system during the nutritional affectations.