Elevated presence of myeloid dendritic cells in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2 inflammation, the mechanism underlying the onset and amplification of this inflammation has not been fully elucidated. Dendritic cells (DCs) are major antigen-presenting cells, central inducers of adaptive immunity and critical regulators of many inflammatory diseases. However, the presence of DCs in CRS, especially in nasal polyps (NPs), has not been extensively studied. OBJECTIVE: The objective of this study was to characterize DC subsets in CRS. METHODS: We used real-time PCR to assess the expression of mRNA for markers of myeloid DCs (mDCs; CD1c), plasmacytoid DCs (pDCs; CD303) and Langerhans cells (LCs; CD1a, CD207) in uncinate tissue (UT) from controls and patients with CRS as well as in NP. We assayed the presence of DCs by immunohistochemistry and flow cytometry. RESULTS: Compared to UT from control subjects (n = 15) and patients with CRS without NP (CRSsNP) (n = 16) and CRSwNP (n = 17), mRNAs for CD1a and CD1c were significantly elevated in NPs (n = 29). In contrast, CD207 mRNA was not elevated in NPs. Immunohistochemistry showed that CD1c(+) cells but not CD303(+) cells were significantly elevated in NPs compared to control subjects or patients with CRSsNP. Flow cytometric analysis showed that CD1a(+) cells in NPs might be a subset of mDC1s and that CD45(+) CD19(-) CD1c(+) CD11c(+) CD141(-) CD303(-) HLA-DR(+) mDC1s and CD45(+) CD19(-) CD11c(+) CD1c(-) CD141(high) HLA-DR(+) mDC2s were significantly elevated in NPs compared to UT from controls and CRSsNP, but CD45(+) CD11c(-) CD303(+) HLA-DR(+) pDCs were only elevated in NPs compared to control UT. CONCLUSION AND CLINICAL RELEVANCE: Myeloid DCs are elevated in CRSwNP, especially in NPs. Myeloid DCs thus may indirectly contribute to the inflammation observed in CRSwNP.

Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the nasal mucosa and paranasal sinuses. This inflammation may result in part from decreased epithelial barrier and innate immune responses, leading to frequent bacterial and fungal colonization. The objectives of this study were to investigate the expression of innate immune proteins of the palate lung and nasal epithelium clone (PLUNC) family in patients with CRS. METHODS: Nasal tissue samples were collected from control subjects and CRS patients with and without nasal polyps. Expression of the members of the PLUNC family was analyzed by real-time PCR. Expression of SPLUNC1 and LPLUNC2 proteins was analyzed by ELISA, immunoblot, and immunohistochemical analysis. RESULTS: Levels of mRNA for most of the members of the PLUNC family were profoundly reduced in nasal polyps (NPs) compared to uncinate tissue from control subjects or patients with CRS. LPLUNC2 and SPLUNC1 proteins were decreased in NPs of patients with CRS compared to uncinate tissue from control subjects. Immunohistochemical data revealed that within submucosal glands of sinonasal tissues, SPLUNC1 and LPLUNC2 were differentially expressed, in serous and mucous cells, respectively. The decrease in the expression of these molecules is probably explained by a decrease in the number of glands in NPs as revealed by correlations with levels of the glandular marker lactoferrin. CONCLUSIONS: Decreased SPLUNC1 and LPLUNC2 in NPs reflect a profound decrease in the number of submucosal glands. Decreased glands may lead to a localized defect in the production and release of glandular innate defense molecules.

Food hypersensitivity and allergic diseases.

Allergic disease is a common cause of morbidity, particularly in young children. The prevalence of allergic disease has increased in the last 20 y in most countries. The sequential order of occurrence of allergy is food hypersensitivity, gastrointestinal manifestations, atopic eczema, asthma and hay fever. A variety of factors increase the risk of allergic disease, for example hereditary predisposition, exposure to 'allergenic' foods and environmental triggers such as house dust mites and tobacco in early life. Prolonged breast feeding, the use of a partial whey hydrolysed formula, delayed introduction of certain 'allergenic foods', and avoidance of inhalant allergens reduces the incidence of eczema and asthma, especially in high-risk infants. These preventive measures are extremely cost-effective and should be adopted widely at the community level.

Nutrition and the immune system from birth to old age.

For millennia, food has been at the center of social events, in times of joy and in times of sorrow. Protein-energy malnutrition is associated with a significant impairment of cell-mediated immunity, phagocyte function, complement system, secretory immunoglobulin A antibody concentrations, and cytokine production. Deficiency of single nutrients also results in altered immune response: this is observed even when the deficiency state is relatively mild. Of the micronutrients, zinc, selenium, iron, copper, vitamins A, C, E and B(6), and folic acid have important influences on immune responses. Overnutrition and obesity also reduce immunity. Low-birth-weight infants have a prolonged impairment of cell-mediated immunity that can be partly restored by providing extra amounts of dietary zinc. In the elderly, impaired immunity can be enhanced by modest amounts of a combination of micronutrients. These findings have considerable practical and public health significance.

Food allergy.

Allergic disease is a major contributor to illnesses and mortality worldwide. Food hypersensitivity is often the first phenomenon in the allergic march that includes gastroenteropathy, eczema, asthma and hay fever. Recent evidence indicates that prevention of food hypersensitivity in early life is associated with reduction in the incidence of eczema and asthma in later childhood. Strategies for prevention include exclusive breast feeding, restriction of mother's diet during lactation, hydrolyzed formula, delayed introduction of allergenic solid foods and reduced exposure to house dust mites and tobacco smoke. This is a highly cost-beneficial and cost-effective approach.

Histological insight into the pathogenesis of severe laryngomalacia.

OBJECTIVE: To correlate clinical and histological findings in patients with laryngomalacia who required surgical intervention. METHODS: Retrospective study of all patients undergoing supraglottoplasty by a single surgeon (MEG) for severe laryngomalacia between October, 1999 and November, 2000. RESULTS: Nine patients were identified, of which seven had clinical evidence of GER. Seven patients had co-existing abnormalities or delays of neuromuscular development including seizure disorder, agenesis of the corpus callosum, obstructive sleep apnea, primary aspiration, a history of apparent life-threatening events, and craniosynostosis. Varying degrees of subepithelial edema and significant dilation of the subepithelial lymphatics were noted in all specimens. Submucosal inflammation was minimal to mild, and intraepithelial inflammation was rare to absent in all sections. No submucosal gland hyperplasia was seen in the samples from any patient. Two specimens contained cuneiform cartilage, both of which were histologically characterized as fibrocartilage. CONCLUSIONS: In this series, the histopathology of tissue excised during the treatment of severe laryngomalacia was dominated by submucosal edema and lymphatic dilation. Further study is needed to investigate comorbidities that may contribute to the need for intervention in children with laryngomalacia.

Effect of vitamin and trace-element supplementation on cognitive function in elderly subjects.

OBJECTIVE: To determine whether supplementation with vitamins and trace elements in modest amounts influences cognitive function in apparently healthy, elderly subjects. METHODS: The study was designed as a randomized, double-blind, placebo-controlled trial. Ninety-six, apparently healthy, independent men and women older than 65 y of age were recruited and randomized to receive a supplement of trace elements and vitamins or a placebo daily for 12 mo. Blood-nutrient levels were estimated at baseline and at the end of the study. The major outcome measure assessed was cognitive function consisting of immediate and long-term memory, abstract thinking, problem-solving ability, and attention. RESULTS: Eighty-six subjects completed the 1-y trial. The supplemented group showed a significant improvement in all cognitive tests (P < 0.001 to 0.05) except long-term memory recall (P > 0.1). Those whose blood-nutrient levels were below the reference standard showed lower responses on cognitive tests. There was no significant correlation between individual nutrient levels and performance on various cognitive function tests. CONCLUSIONS: Cognitive functions improved after oral supplementation with modest amounts of vitamins and trace elements. This has considerable clinical and public health significance. We recommend that such a supplement be provided to all elderly subjects because it should significantly improve cognition and thus quality of life and the ability to perform activities of daily living. Such a nutritional approach may delay the onset of Alzheimer's disease.

Histological characterization of the thyroglossal tract: implications for surgical management.

OBJECTIVES: In the current report, we characterized the relationship between the central hyoid bone and the thyroglossal tract and determined the prevalence of ectopic thyroid follicles in the adjacent soft tissues. STUDY DESIGN: Retrospective pathological analysis. METHODS: The resected specimens from 104 patients who underwent a modified Sistrunk procedure with wide-field dissection were retrospectively analyzed. Under light microscopy, serial sections were examined to determine whether the thyroglossal tract passed anterior to, posterior to, or within the hyoid bone. Specimens were also examined for the presence of thyroid follicles in the periductal and pericystic soft tissues. RESULTS: In 50 cases (48%), the tract position in relation to the hyoid bone could not be identified secondary to extensive arborization, marked inflammation, specimen fragmentation or a combination of these. Thyroid follicles were observed in 9 (18%) of these specimens. In the remaining 54 cases (52%) the tract was located anterior to the central arch of the hyoid bone in 39 (72%) and posterior to it in 15 (28%). Thyroid tissue was observed in 46% of specimens (P =.004), regardless of whether the tract was anterior or posterior. CONCLUSIONS: These results demonstrate that tract position often cannot be defined, but when a portion is dominant, it is likely to be anterior to the hyoid bone. Ectopic thyroid tissue can be found in almost 50% of specimens when the tract position is identifiable. With appropriate surgical management, a recurrence rate of less than 4% can be expected, despite the presence of ductule multiplicity, marked inflammation, tract position posterior to the hyoid bone, and ectopic thyroid follicles.

Nutritional status of young female elite gymnasts.

The purpose of this study was to evaluate the nutritional status of a group of 10 young female elite gymnasts aged 13-17 years, who do a physical exercise of 48 h/wk. Assessment included dietary intake for 7 days, body mass index, ideal body weight, and skinfold thickness. In addition, the number of total leukocytes, total lymphocytes and lymphocyte subsets CD2, CD3, CD4, CD8, CD19 and CD56 were counted. The results were compared with a control group consisting of 50 volunteer students doing less than 12 h/wk of physical exercise, who were matched by sex, age, and sociocultural level. The total weekly calorie intake was lower in gymnasts than in controls; gymnasts showed a higher calorie intake from dietary protein together with a lower calorie intake from lipid and carbohydrate sources in comparison with controls. All the anthropometric parameters, except height which was not different in the two groups, were lower in gymnasts than in controls. The lymphocyte and leukocyte counts were also lower in gymnasts in relation to controls, except CD19 and CD56 subsets which were similar in both groups. It is suggested that gymnasts are at risk of malnutrition, which when compounded with intense physical exercise could lead to immunosuppression in these athletes.

Food allergy and nutrition in early life: implications for later health.

Allergic diseases are a common cause of illness in most industrialized countries. Diet during early childhood is an important determinant of the development of allergy, particularly in high-risk infants who have a parental history of atopy. Maternal avoidance of highly-allergenic foods during pregnancy and lactation, prolonged exclusive breast-feeding, the use of a hydrolysed milk formula, and delayed introduction of dairy products, eggs, fish, nuts and soybean are associated with a lower incidence of allergic symptoms and signs. These beneficial effects are observed for as long as 18 years of age. Similarly, nutrition and physical growth are important factors that influence immunocompetence and morbidity due to infections. Small-for-gestational age low-birth-weight infants show prolonged impairment of cell-mediated immunity, antibody responses and phagocyte function. Recent studies indicate the beneficial effect of moderate amounts of Zn given in the first 6 months of life. Thus, diet and nutrition in early life are crucial for the development of allergic and infectious disease throughout childhood and into adulthood.

Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019).

OBJECTIVE: To determine the effects of dietary consumption of Bifidobacterium lactis (strain HN019, DR10TM) on natural immunity. DESIGN: A randomized, double blind, placebo-controlled clinical trial. SETTING: Janeway Medical Centre, Memorial University, St Johns, Newfoundland. SUBJECTS: Twenty-five healthy elderly volunteers (median age 69 y; range 60-83 y). INTERVENTIONS: Twelve control subjects consumed 180 ml low-fat/low-lactose milk twice daily for a period of 6 weeks; 13 test subjects consumed milk supplemented with 1.5x1011 colony-forming units of B. lactis twice daily. Indices of natural immunity, including interferon production, phagocytic capacity and phagocyte-mediated bactericidal activity, were determined via peripheral blood at 0, 3, 6 and 12 weeks post-trial commencement. RESULTS: Subjects who consumed milk containing B. lactis for 6 weeks produced significantly enhanced levels of interferon-alpha, upon stimulation of their peripheral blood mononuclear cells in culture, in comparison to the placebo control group who received milk alone. There were also significant increases in polymorphonuclear cell phagocytic capacity among test group subjects, following consumption of milk supplemented with B. lactis, while individuals who consumed B. lactis-supplemented milk or milk alone showed enhanced phagocyte-mediated bactericidal activity. CONCLUSIONS: The results demonstrate that dietary consumption of B. lactis HN019 can enhance natural immunity in healthy elderly subjects, and that a relatively short-term dietary regime (6 weeks) is sufficient to impart measurable improvements in immunity that may offer significant health benefits to consumers. SPONSORS: Financial support for this project was provided by the New Zealand Dairy Board.

Nutrition and immunology: from the clinic to cellular biology and back again.

Diet and immunity have been known to be linked to each other for centuries. In the last 30 years systematic studies have confirmed that nutrient deficiencies impair immune response and lead to frequent severe infections resulting in increased mortality, especially in children. Protein-energy malnutrition results in reduced number and functions of T-cells, phagocytic cells and secretory immunoglobulin A antibody response. In addition, levels of many complement components are reduced. Similar findings have been reported for moderate deficiencies of individual nutrients such as trace minerals and vitamins, particularly Zn, Fe, Se, vitamins A, B6, C and E. For example, Zn deficiency is associated with profound impairment of cell-mediated immunity such as lymphocyte stimulation response, decreased CD4+:CD8+ cells, and decreased chemotaxis of phagocytes. In addition, the level of thymulin, which is a Zn-dependent hormone, is markedly decreased. The use of nutrient supplements, singly or in combination, stimulates immune response and may result in fewer infections, particularly in the elderly, low-birth-weight infants and malnourished critically-ill patients in hospitals. The interactions between nutrition and the immune system are of clinical, practical and public health importance.

[Effect of the diet on the nutritional status of ballerinas: immunologic markers]. / Influencia de la dieta en el estado nutricional de bailarinas: marcadores inmunológicos.

UNLABELLED: Athletes have special nutritional needs that will vary with sex, age, body composition and most importantly by the type, intensity, frequency and duration of the physical exercise. However the diet of certain groups of athletes such as ballet dancers is inadequate due to overly restrictive habits as a consequence of their obsession with losing or maintaining a low body weight that reflects an aesthetic preference for thinness. Physical exercise implies energy expenditure and thus, an increase in the energy intake is required to avoid possible situations of malnutrition. Both a negative energy balance and physical exertion have been shown to induce immunological changes which have been implicated as a possible explanation for increased susceptibility to illness and infections. OBJECTIVE: To find out the influence of a restricted energy intake on the immune system of 14 ballet dancers (20-25 h/w) in comparison with a control sedentary group (n = 23) by evaluating dietetic, anthropometric and some immunological parameters. RESULTS: Ballet dancers consumed a hypocaloric diet (mean: 1555 kcal), the energy intake being significantly lower than in the control group. None of both groups showed a similar calorie profile to the recommended intake for Spanish population, especially fat percentage was higher than it should. Regarding weight, ideal body weight and BMI values, no significant differences were shown between both groups. However, all the skinfolds thickness and the sum of skinfolds were significantly lower in ballet dancers than in controls. Leukocytes, lymphocytes and all lymphocyte subset counts were lower in ballet dancers in comparison with controls. CONCLUSIONS: In view of these results, ballet dancers may suffer from an impaired nutritional status, determined by a depletion of anthropometric and immunological parameters. The nutritional requirements for this population should be increased in order to compensate their high-energy expenditure, avoid a negative energy balance and lessen the nutritional damage.

Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men.

The purpose of this study was to examine the effects of feeding docosahexaenoic acid (DHA) as triacylglycerol on the fatty acid composition, eicosanoid production, and select activities of human peripheral blood mononuclear cells (PBMNC). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of Western Human Nutrition Reach Center. Four subjects (control group) were fed the stabilization diet throughout the study; the remaining seven subjects were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg D alpha-tocopherol acetate per day. PBMNC fatty acid composition and eicosanoid production were examined on day 30 and 113; immune cell functions were tested on day 22, 30, 78, 85, 106, and 113. DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding. These parameters remained unchanged in the subjects fed the control diet. B-cell functions as reported here and T-cell functions that we reported previously were not altered by DHA feeding. Our results show that inhibitory effects of DHA on immune cell functions varied with the cell type, and that the inhibitory effects are not mediated through increased production of PGE2 and LTB4.

Nutrition and the immune system: an introduction.

Nutrition is a critical determinant of immune responses and malnutrition the most common cause of immunodeficiency worldwide. Protein-energy malnutrition is associated with a significant impairment of cell-mediated immunity, phagocyte function, complement system, secretory immunoglobulin A antibody concentrations, and cytokine production. Deficiency of single nutrients also results in altered immune responses: this is observed even when the deficiency state is relatively mild. Of the micronutrients, zinc; selenium; iron; copper; vitamins A, C, E, and B-6; and folic acid have important influences on immune responses. Overnutrition and obesity also reduce immunity. Low-birth-weight infants have a prolonged impairment of cell-mediated immunity that can be partly restored by providing extra amounts of dietary zinc. In the elderly, impaired immunity can be enhanced by modest amounts of a combination of micronutrients. These findings have considerable practical and public health significance.

Food hypersensitivity and allergic disease: a selective review.

Food intolerance can be caused by immunologic, pharmacologic, toxic, infectious, idiosyncratic, metabolic, and neuropsychologic processes. Food allergy denotes an adverse reaction to food or food additives in which an underlying immunologic mechanism can be shown. Its incidence in young children is approximately 1.3% and among adults is 0.3%. Parental history of atopy is a significant causal factor. In addition, exposure to common allergenic foods in infancy increases risk. For these reasons, exclusive breast-feeding and maternal avoidance of peanut, egg, fish, and dairy products during lactation has been recommended and shown to reduce the occurrence of food allergy. Wheat, egg, and fish should not be introduced until the infant is aged > 12 mo and peanut until the age of 36 mo. These measures and other environmental precautions can be expected to reduce the cumulative prevalence of allergy.