Perinatal PUFA intake affects leptin and oral tolerance in neonatal rats and possibly immunoreactivity in intrauterine growth retardation in man.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Marina Korotkova
Publications and source records attributed to Marina Korotkova.
Effects of antirheumatic treatments on the prostaglandin E2 biosynthetic pathway.
OBJECTIVE: Microsomal prostaglandin E synthase 1 (mPGES-1) is up-regulated in experimental arthritis and markedly expressed in synovial tissue biopsy samples from patients with rheumatoid arthritis (RA). This study was carried out to determine the effects of tumor necrosis factor (TNF) blockers and glucocorticoids on mPGES-1 and cyclooxygenase (COX) expression, as well as biosynthesis of PGE(2) in rheumatoid joints. METHODS: In vitro effects of TNF blockers and dexamethasone on the PGE(2) biosynthetic pathway were examined in RA synovial fluid mononuclear cells (SFMCs) by flow cytometry. PGE(2) levels in culture supernatants were measured by enzyme immunoassay. Expression of enzymes responsible for PGE(2) synthesis ex vivo was evaluated by immunohistochemistry in synovial biopsy samples obtained from 18 patients before and after treatment with TNF blockers and from 16 patients before and after intraarticular treatment with glucocorticoids. Double immunofluorescence was performed using antibodies against mPGES-1, COX-1, COX-2, and CD163. RESULTS: Double immunofluorescence revealed that mPGES-1 and COX-2 were colocalized in SFMCs as well as in RA synovial tissue cells. The addition of either TNF blockers or dexamethasone suppressed lipopolysaccharide-induced mPGES-1 and COX-2 expression in synovial fluid monocyte/macrophages in vitro and decreased the production of PGE(2). Intraarticular treatment with glucocorticoids significantly reduced both mPGES-1 and COX-2 expression in arthritic synovial tissue ex vivo. The number of COX-1-expressing cells in synovial tissue was also significantly decreased by glucocorticoid treatment. In contrast, neither mPGES-1 nor COX-2 expression in synovial tissue was significantly suppressed by anti-TNF therapy. CONCLUSION: These data are the first to demonstrate the effects of antirheumatic treatments on mPGES-1 expression in RA and suggest that the inhibition of PGE(2) biosynthesis, preferably by targeting mPGES-1, might complement anti-TNF treatment for optimal antiinflammatory results in RA.
Adult↗
Cost-effectiveness of alendronate in the prevention of osteoporotic fractures in Danish women.
Pharmacological interventions for osteoporosis may reduce morbidity and mortality, but they incur additional health care costs. The aim was to quantify the additional costs and health benefits of prescribing alendronate 10 mg and calcium/vitamin D daily for 71-year-old women with a fracture risk twice that of the population average in stead of calcium/vitamin D alone. A state transition model based primarily on Scandinavian data was developed. Women were followed from age of 71 years until 100. Alendronate was assumed to reduce the fracture risk by 50%. Health benefits from the interventions were expressed in terms of life years, quality adjusted life years, and fractures avoided. Societal costs were estimated using literature estimates and Danish tariffs. All costs were measured in 2002 Danish Kroner (DKK). Future costs and benefits were discounted at 5% per year. The incremental cost per QALY gained was DKK125,000 while the cost per life year gained was DKK 374,000. The use of alendronate was cost-saving when 1) the treatment was extended to five years, 2) the risk of fracture was four times the population average, 3) the effect of alendronate was assumed to persist for three years after discontinuation of treatment, 4) a greater proportion had severe sequelae after a hip fracture, or 5) the start of therapy was delayed until age of 77 years. In conclusion, the use of alendronate compares well with other well established therapies in terms of cost-effectiveness in older women with high risk of fracture.
Aged↗
Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids.
Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.
Aging↗
Modulation of neonatal immunological tolerance to ovalbumin by maternal essential fatty acid intake.
The present study examines whether dietary essential fatty acid (EFA) intake influences the induction of oral tolerance to ovalbumin (OA) in neonatal and adult rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet supplemented (S) with EFA (7% soybean oil), or a diet deficient (D) in EFA (7% hydrogenated lard). The rat offspring were subsequently exposed to OA either via the milk at 10-16 days (neonatal rats), or as adults via the drinking water at 7-9 wk of age. Oral administration of OA to the adult rats lead to suppression of the delayed-type hypersensitivity (DTH) reactivity and IgG antibody response against OA, which was not influenced by their diets. In the offspring of the dams fed the D diet antigen exposure via the milk resulted in suppression of the serum antibody levels and DTH reaction against OA indicating induction of oral tolerance. Higher transforming growth factor beta (TGF-beta) mRNA levels in the draining lymph nodes suggested this to be mediated by regulatory T cells. In contrast, OA exposure of the dams fed the S diet did not result in a suppressed OA response of their offspring. Thus, the quality of FA ingested by the mother may have effects on the development of immunological tolerance to dietary antigens in the offspring. Our results might have importance for the understanding of the increase in allergy related to the Western type of diet.
Age Factors↗
Antigen presentation and processing in the intestinal mucosa and lymphocyte homing.
OBJECTIVE: The mucosal surface of the gastro-intestinal tract is our major interface to the environment. Much of the control of the immune response to the myriads of antigen present at this interface is mediated by professional antigen-presenting dendritic cells (DCs). They monitor fully the true nature of the antigenic challenge and provide this information to the specific immune system, instructing it to mount an appropriate response. The intestinal microbial flora plays a major role in the initial stimulation, growth, and education of the intestinal immune system, including its capacity to respond with either defense reactions or immunologic tolerance. DATA SOURCES: To review the recent literature on the process of antigen sampling, processing, presentation, and initiation of immune recognition that take place on mucosal surfaces and their draining lymph nodes, especially the intestinal mucosa. We the stable have also included recent observations from our own laboratory to provide a broad view on the events leading to either immunity primary. or tolerance to environmental antigens. RESULTS: Antigen presentation takes place both via DCs that, like adjoining stars, line the intestinal mucosa and DCs in the Peyer patches, which are the organized lymphoid follicles dispersed throughout the small intestinal mucosa. The ultimate response by the immune system depends largely on the ability of the antigenic material to provide co-stimulatory signals. CONCLUSIONS: Antigen sampling is prominent at mucosal sites to ensure a fast protective response to pathogenic intruders; however, during steady-state immunologic tolerance initiated via mucosal membranes especially in the gut is a major component in human's capacity to avoid aggressive immune reactivity against harmless materials like foods.
Animals↗
Breast-feeding, infant formulas, and the immune system.
OBJECTIVE: Breast-feeding provides many advantages to the offspring, but presently there is an ongoing debate whether or not it prevents allergy any better than certain formulas. This report reviews the mechanisms involved and discusses how breast-feeding may protect against allergy. DATA SOURCES: The review builds on an internet-based literature search in addition to our own data. RESULTS: Human milk is the food best adapted to the needs of the offspring, also because it provides efficient protection against infections and actively stimulates the development of the infant's own immune system. The major host defense system is provided via the secretory IgA antibodies produced in the mammary glands by lymphocytes, which have migrated there from the mother's gut mucosa. Therefore, these antibodies in the milk are primarily directed against the microbes in the mother's gut and her food proteins. As a result, breast-feeding starting directly after delivery will provide an excellent defense against the microbes normally meeting the neonate and needed to induce development of its immune system. The milk also contains numerous components, which seem to enhance the infant's host defense as well as capacity to develop tolerance, helping to avoiding allergic reactivity to foods, etc. CONCLUSIONS: Several studies show that breast-feeding prevents allergic diseases, but there are also good disagreeing studies. Supported by animal data, it seems that protection is enhanced in areas with more advantageous fat intake, inter alia lower ratio of n-6/n-3 fatty acids. Breast-feeding seems to protect against future development of allergic diseases, but possibly less so in countries with an untoward maternal fat intake.
Animals↗
The transfer of immunity from mother to child.
The newborn's immune system grows fast from a small size at birth by exposure primarily to the intestinal microflora normally obtained from the mother at and after birth. While building up its immune system, the infant is supported by the transplacental IgG antibodies, which also contain anti-idiotypic antibodies, possibly also actively priming the offspring. The second mode of transfer of immunity occurs via the milk. Numerous major protective components, including secretory IgA (SIgA) antibodies and lactoferrin, are present. The breastfed infant is better protected against numerous common infections than the non-breastfed. Breastfeeding also seems to actively stimulate the infant's immune system by anti-idiotypes, uptake of milk lymphocytes, cytokines, etc. Therefore, the breastfed child continues to be better protected against various infections for some years. Vaccine responses are also often enhanced in breastfed infants. Long-lasting protection against certain immunological diseases such as allergies and celiac disease is also noted.
Female↗
Immune system modulation by human milk.
Explore the source record for details and available documents.
Humans↗
The role of breastfeeding in prevention of neonatal infection.
The immune system of the human newborn is of very limited size. It expands rapidly, especially due to the exposure to the gut microflora. Normally the newborn is colonized with microbes from the mother's intestinal flora at and after delivery. The many defence factors of the mother's milk include large amounts of secretory IgA antibodies produced by lymphocytes which have migrated from the mother's gut to the mammary glands. Therefore the SIgA antibodies are mainly directed against the mother's previous and recent gut microflora. Thus breastfeeding modulates the early exposure of the neonate's intestinal mucosa to microbes and limits bacterial translocation through the gut mucosa. This may be a major reason why breastfeeding protects efficiently against neonatal septicaemia, as well as several other infections. The defence factors of the milk prevent infections already at the mucosal level. The transplacentally obtained maternal IgG antibodies protect primarily in tissues and do so at the cost of cytokine-induced clinical symptoms, tissue engagement and high energy consumption.
Bacterial Translocation↗
Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet.
The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal development. We have previously shown that leptin levels in suckling rats are reduced by maternal PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and (n-6) PUFA on the leptin content in rat milk and serum leptin levels in suckling pups. For the last 10 days of gestation and throughout lactation, the rats were fed an isocaloric diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet), or soybean oil (n-6/n-3 diet). Body weight, body length, inguinal fat pad weight, and adipocyte size of the pups receiving the n-3 diet were significantly lower during the whole suckling period compared with n-6/n-3 fed pups. Body and fat pad weights of the n-6 fed pups were in between the other two groups at week one, but not different from the n-6/n-3 group at week 3. Feeding dams the n-3 diet resulted in decreased serum leptin levels in the suckling pups compared with pups in the n-6/n-3 group. The mean serum leptin levels of the n-6 pups were between the other two groups but not different from either group. There were no differences in the milk leptin content between the groups. These results show that the balance between the n-6 and n-3 PUFA in the maternal diet rather than amount of n-6 or n-3 PUFA per se could be important for adipose tissue growth and for maintaining adequate serum leptin levels in the offspring.
Adipocytes↗
Maternal dietary intake of essential fatty acids affects adipose tissue growth and leptin mRNA expression in suckling rat pups.
We have previously shown that maternal intake of essential fatty acids during late gestation and lactation affects the level of serum leptin in pups. The aim of the present study was to investigate the effect of dietary essential fatty acids on leptin content in the milk of rat dams and leptin expression in white adipose tissue of pups during the suckling period. During late gestation and throughout lactation, rats were fed a control or an essential fatty acid-deficient (EFAD) diet. Milk of the EFAD dams contained more saturated and less polyunsaturated fatty acids compared with the control dams. Milk leptin levels were higher in the EFAD dams than in the control dams at 3 wk of lactation. The weight of inguinal white adipose tissue depots and the serum leptin levels of the EFAD pups were significantly lower than in the control pups during the whole suckling period. In addition, semiquantitative reverse transcriptase-PCR analysis of leptin mRNA levels in inguinal white adipose tissue showed a reduction in the EFAD pups compared with the control pups at 3 wk of age. We conclude that maternal dietary essential fatty acid intake affects serum leptin levels in pups by regulating both the amount of adipose tissue and the leptin mRNA expression.
Adipose Tissue↗
Breast-feeding, a complex support system for the offspring.
The newborn has an immune system, very limited in size at birth and its postnatal expansion and maturation takes time. In the meantime the transplacental IgG antibodies from the mother play an important role for the protection of the infant. However, these antibodies act in tissues and induce inflammation and are energy-consuming. In contrast, the milk secretory IgA antibodies stop microbes already on the mucosa preventing infection, tissue engagement and energy loss. In addition, the milk contains many protective factors such as lactoferrin and oligosacharides functioning as analogues for microbial receptors preventing mucosal attachment, the initial step of most infections. As a result, breast-feeding significantly reduces the risk of neonatal septicemia, respiratory tract infections, otitis media, diarrhea, urinary tract infections, infection-induced wheezing and necrotizing enterocolitis. Via several mechanisms it seems that human milk can actively stimulate the immune system of the breast-fed infant. This reduces the risk of infections like otitis media, respiratory tract infections, diarrhea and infection-induced wheezing for several years after the termination of breast-feeding. Furthermore, it seems that breast-feeding decreases the risk of attracting celiac disease and allergic diseases. The latter has been much debated, but a recent critical review of published reports gives good support for long-term protection of allergic diseases, especially in high-risk children.
Breast Feeding↗