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.

Antibody formation in first and second generation offspring of nutritionally deprived rats.

Prolonged partial restriction of calorie intake in young rats results in reduced growth, involution of lymphoid organs, and lymphopenia. After immunization with sheep red blood cells, the number of antibody-forming cells in the spleen and serum hemolysin titers are markedly reduced. The effect is more pronounced on the primary response and on immunoglobulin G antibody-forming cells. Significant impairment of antibody formation is detectable in the first (F1) and second (F2) generation offspring of starved Fo mothers.

Immune response in overnutrition.

Nutritional modulation of the immune response can be demonstrated both in nutritional deficiency and in obesity. A proportion of obese adolescents and adults showed a variable impairment of cell-mediated immune responses in vivo and in vitro and reduction of intracellular bacterial killing by polymorphonuclear leukocytes. Immunological changes correlated with subclinical deficiencies of iron and zinc, and therapy with these micronutrients for 4 weeks resulted in improvement in immunological responses. In genetically obese mice, the number of mononuclear cells and Thy 1.2-positive lymphocytes in the thymus and the spleen is less compared with that in lean controls. The plaque-forming antibody response is reduced. Natural killer cell activity is increased. Cytotoxic response of spleen cells of obese animals immunized in vivo was markedly lower than that of lean controls, whereas the same response after in vitro sensitization was normal. These data point to the importance of metabolic and nutritional factors in the pathogenesis of altered immunocompetence.

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.

Cell-mediated immunity in genetically obese C57BL/6J ob/ob) mice.

The thymus and spleen of genetically obese (C57BL/6J ob/ob) mice weighed less and contained fewer mononuclear cells and Thy 1.2-positive lymphocytes compared with findings in lean controls. The number of splenic antibody forming cells, particularly IgG-producing lymphocytes, was reduced. There was a marked increase in natural killer cell activity and a slight increase in antibody-dependent cell-mediated cytotoxicity in the obese animals. Cytotoxic response of spleen cells of obese mice immunized in vivo was markedly lower than that of lean controls, whereas the generation of T killer cells against alloantigens after in vitro immunization was unimpaired, which points to a deleterious "microenvironment" in obesity. It is suggested that metabolic, nutritional, and endocrine changes in obesity may contribute to altered immunocompetence.

Single nutrient deficiency and cell-mediated immune responses. I. Zinc.

The thymus of rats provided zinc-deficient diet weighed less than the thymus of animals fed zinc-containing control diet. The antibody-forming cell response in the spleen was reduced. Cytotoxic response of spleen cells of zinc-deficient mice immunized in vivo was decreased whereas after sensitization in vitro the response was comparable to that seen in zinc-replete animals. Natural killer cell activity and antibody-dependent cell-mediated cytotoxicity were increased, particularly the former. These observations suggest that dietary zinc intake is an important factor modulating cell-mediated immune responses.

Antibody affinity and immune complexes after immunization with tetanus toxoid in protein-energy malnutrition.

Protein-energy malnutrition reduced the affinity of antibody to tetanus toxoid, particularly after primary immunization. The effect on antibody affinity was more marked in patients with hypoproteinemia than in those with marasmus. Hemagglutinating antibody levels were comparable in undernourished and well-nourished groups. Circulating immune complexes were detected in eight of 21 children with protein-energy malnutrition and in one of the controls. Differences in antibody affinity in malnutrition may be an important determinant of altered host resistance and of complications of disease in nutritional deficiency.

Anaphylactoid reaction to methylprednisolone pulsed therapy for multiple sclerosis.

A further case of anaphylactoid reaction to methylprednisolone is reported. The occurrence of allergic reactions to steroids is reviewed, and suggestions for management of pulsed IV methylprednisolone therapy are made.

Serum thymic hormone activity and cell-mediated immunity in healthy neonates, preterm infants, and small-for-gestational age infants.

Groups of healthy, small-for-gestational age (SGA) and preterm appropriate-for-gestational age (AGA) infants were studied at birth, 1 month, 3 months, and 12 months of age. Serum thymic hormone (TH) activity was assayed, the number of T lymphocytes in the peripheral blood was counted, and in vitro lymphocyte stimulation responses to phytohemagglutinin (PHA) were evaluated. TH activity was decreased in 1-month-old SGA infants. T cells were reduced in all low birth weight infants; the number reverted to normal by 3 months of age in preterm AGA infants, whereas it remained low for at least 12 months in the SGA group. Lymphocyte stimulation response was decreased in low birth weight infants; the extent of depression paralleled reduction in T lymphocyte number. These observations indicate that cell-mediated immunity is impaired in low birth weight newborns and reduced TH activity may be one of the pathogenetic factors involved. Persistent depression of immunocompetence may underlie the increased susceptibility of SGA infants to infection-related morbidity and mortality.

Lymphocyte subpopulations in human malnutrition: cytotoxic and suppressor cells.

Lymphocytes in the peripheral blood of young children with protein-calorie undernutrition were evaluated for surface markers and function. Thymus-dependent lymphocytes were reduced and the immunoglobulin-bearing B lymphocytes were unchanged. The relative proportion of the remaining "null" lymphoid cells was increased. Null cells and, to a lesser extent, B lymphocytes showed cytotoxic activity against xenogeneic target cells and suppressed phytohemagglutinin-induced DNA synthesis by normal T lymphocytes. It is suggested that these alterations in lymphoid subpopulations contribute to depressed cell-mediated immunity in malnutrition.

Effect of zinc administration on cadmium-induced suppression of natural killer cell activity in mice.

Natural killer (NK) cells play an important role in immune surveillance against viral infections and neoplasms. The effect of cadmium with or without zinc on mouse spleen NK cell activity was studied. Six-week-old male C57BL/6 mice were given drinking water containing either 50 ppm cadmium, 50 ppm cadmium together with 500 ppm zinc, or 500 ppm zinc. A fourth group receiving no additional cadmium or zinc served as control. After 3 weeks of treatment, the mice were killed, splenic lymphocytes isolated and cultured with 51Cr-labelled YAC-1 target cells for 4 and 12 h in a ratio of 50:1. The percentage of target cell lysis was measured to assess NK cell activity. In the 12-h assay, cadmium-treated animals had significantly lower NK cell activity than controls. Concurrent zinc administration prevented the suppression. In the 4-h assay, a similar trend was observed. Between 4 and 12 h, NK cell activity increased significantly in control and zinc-treated groups, but not in those receiving cadmium. The results suggest that a relatively low dose of cadmium suppresses NK cell activity, which can be prevented by a moderately large dose of zinc.

Effect of two feeding formulas on immune responses and mortality in mice challenged with Listeria monocytogenes.

Cell-mediated immunity and natural killer cells play an important role against facultative intracellular organisms. The effect of two commercially available tube feeding formulas used for patients with acute or chronic debilitating and life-threatening illnesses was studied in mice challenged with Listeria monocytogenes. C57BL/6 X DBA/2 F1 hybrid mice were given ad libitum access to one of two formulas or to chow. Sixty mice in each of the feeding groups were challenged with 4.8 X 10(3) organisms intraperitoneally. Mortality was significantly less in animals fed Impact, a formula enriched with arginine, RNA and selected fatty acids. This was associated with reduced number of viable organisms in the spleen on day 7 after challenge. There was no difference in the spleen/body weight index between the different groups. Delayed cutaneous hypersensitivity was slightly higher in the Impact group but this was not statistically significant. Natural killer cell activity was significantly higher in the Impact group compared with the other two feeding regimens. These observations suggest that selective manipulation of the composition of tube feeding formulas may have a significant impact on immune responses and on morbidity and mortality following infectious challenge.

Immunological aspects of human milk.

PIP: The general decline in breastfeeding in most parts of the world has become a major health concern in view of the many physiological, biochemical, psychological, cultural, and economic benefits of breastfeeding for a few months after birth. A review of the immunologic aspect of breastfeeding shows that a spectrum of interacting specific and nonspecific antimicrobial resistance factors found in the human milk (e.g., physicochemical properties, immunoglobulins, iron-binding protein, interferon, polymorphonuclear leukocytes, and macrophages) are responsible for the lowered incidence of infections, particularly gastrointestinal and respiratory infections, allergic disorders (e.g., infantile eczema), necrotizing enterocolitis, and sudden infant death syndrome among breastfed babies. Possible disadvantages of breastfeeding are 1) poliovirus antibodies in human milk may interfere with live attenuated poliovirus vaccine; and 2) possible infection of breastfed infant with microorganisms found in human milk (e.g., Hepatitis B surface antigen and rubella virus). In view of the significant advantages of breastfeeding for the infant, breastfeeding all newborns during the 1st year of life is recommended.^ieng

Chemotaxis, random mobility, and mobilization of polymorphonuclear leucocytes in malnutrition.

Neutrophil mobilization following administration of Pseudomonas polysaccharide was significantly reduced in malnutrition, especially during infection. The random mobility of polymorphonuclear leucocytes (PMNs) was slightly decreased in undernutrition. Chemotactic migration of PMNs was depressed and correlated more with the presence of infection than with nutritional deficiency. It is possible that these abnormalities of PMN mobilization and mobility in malnourished individuals contribute to suboptimal amount, kinetics, and pattern of tissue inflammatory response to bacteraemic challenge.

A study of erythrocyte fatty acids, adenosinetriphosphatase and acetylcholinesterase in cystic fibrosis.

1. The proportions of both saturated and polyunsaturated fatty acids were measured in the erythrocytes in Cystic Fibrosis (CF) patients along with two membrane bound enzymes ATPase and acetylcholinesterase. Linoleic acid was found to be significantly decreased and arachidonic acid increased in CF patients. The proportion of saturated fatty acids were not significantly different from the controls. Only adenosinetriphosphatase activity was found to be reduced and not acetylcholinesterase in CF patients.

A study of the salivary glycoprotein in cystic fibrosis patients and controls: fucose incorporation and protein pattern.

The incorporation of fucose to glycoprotein acceptors prepared from the saliva of Cystic Fibrosis (CF) patients was compared with the incorporation into acceptors from controls. The CF acceptor glycoprotein incorporated significantly more fucose in the presence of either patients' or control plasma. The fucosyl transferase activity in the patients' plasma was not significantly different from controls. Fucosidase activity was similar also for both groups. The protein bands of the acceptor glycoproteins from the patients' saliva differed from those of the control in number and electrophoretic mobility. On the basis of these studies of fucose incorporation we propose that glycoprotein in the salivary secretion of CF patients are qualitatively different from normal.

Indian childhood cirrhosis: genealogic data, alpha-foetoprotein, hepatitis antigen and circulating immune complexes.

Indian childhood cirrhosis is a significant cause of morbidity and mortality in young children in India. One hundred patients with ICC, 66 boys and 34 girls, were studied. Pedigree analysis yielded a segregation ratio of 0-2196, suggestive of an autosomal recessive inheritance. Serum alpha1-antitrypsin level was normal. Serum alpha-foetoprotein (AFP) concentration was increased in all the patients, parents and in some siblings. Serum immunoglobulins G, A, M, and D were elevated. Haemolytic complement and C3 were low. Electrophoretically altered complement components were detected in 36% of patients. There was an inverse relationship between C3 concentration and immunoconglutinin titre. Circulatingimmune complexes were detected in the sera of six out of ten patients who had significant proteinuria. Hepatitis B surface antigen (HBsAg) was present in the serum, ascitic fluid, saliva, urine and faeces of ICC patients more frequently than in controls. HBsAb was detected less often. Lymphocyte response to HBsAg was impaired. The first-degree relatives had a higher incidence of HBsAg and HBsAb than healthy controls. It is suggested that ICC occurs in infants with an inherited hepatocyte vulnerability and that one of the precipitating causes of liver cell necrosis is infection with hepatitis virus(es). The consequent immunologic epiphenomena contribute to progressive hepatic damage ending in death.

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.