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Biomedical subjects

S L Prescott

Publications and source records attributed to S L Prescott.

At least 19 recordsLinked to original sources
PubMed2004

Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition.

OBJECTIVE: The aim of this study was to assess the effects of fish oil supplementation in pregnancy on maternal erythrocyte fatty acid composition at different stages of pregnancy and in the post-partum period, and on neonatal erythrocyte fatty acid composition. DESIGN: A double-blind, randomised, placebo-controlled study. SETTING: : Subiaco, Western Australia. SUBJECTS: In all, 98 women booked for delivery at St John of God Hospital, Subiaco, were recruited from private rooms of obstetricians. In total, 83 women and their healthy full-term babies completed the study. INTERVENTION: Women received either 4 g of fish oil (n=52) (56% docosahexaenoic acid (DHA) and 28% eicosapentaenoic acid (EPA) or placebo (olive oil) (n=46) per day from 20 weeks gestation until delivery. MAIN OUTCOME MEASURES: Erythrocyte phospholipid fatty acids were measured in maternal peripheral blood at 20, 30 and 37 weeks of pregnancy and at 6 weeks post partum, and from cord blood collected at birth. RESULTS: Compared to the control group, maternal EPA and DHA were significantly higher in the fish oil group at 30 and 37 weeks gestation, and remained elevated at 6 weeks post partum (P<0.001). The proportions of n-6 polyunsaturated (arachidonic acid, 22:3n-6 and 22:4n-6) were significantly lower in the fish oil supplemented group at the same time periods (P<0.001). Similarly, the proportions of EPA and DHA were significantly higher (P<0.001), and those of n-6 polyunsaturated fatty acids arachidonic acid, 20:3n-6, 22:3n-6 and 22:4n-6 were significantly lower (P<0.001), in erythrocytes from neonates in the fish oil group, compared to those in the control group. CONCLUSION: Fish oil supplementation from 20 weeks of pregnancy until birth is an effective means of enhancing n-3 fatty acid status of both mothers and neonates. Furthermore, the changes in maternal erythrocyte fatty acid composition are retained until at least 6 weeks post partum. It is essential to assess the effects of concomitant decreases in arachidonic acid status before any dietary recommendations can be made. SPONSORSHIP: The study was supported by grants from the NH & MRC and Raine Medical Research Foundation, Australia.

Adult↗
PubMed2004

The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition.

BACKGROUND: Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development. OBJECTIVE: To determine if changes in breast milk omega-3 polyunsaturated fatty acid (n-3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk. METHOD: In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n-3 PUFA) (n = 40) or 4 g olive oil capsules (n = 43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post-partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) were quantitated by ELISA or time resolved fluorescence (TRF). RESULTS: Omega-3 docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels were significantly higher (P < 0.001) in breast milk from women supplemented with fish oil (n = 33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n = 40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n-6) levels were significantly lower (P = 0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA (P = 0.046) and 22:5n-3 (P = 0.003), but inversely correlated with linoleic acid (LA; 18:2n-6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n-3 (P=0.009). Cytokines involved in IgA synthesis (IL-10 and IL-6) were also significantly correlated with both IgA and n-3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups. CONCLUSION: Supplementation with fish oil during pregnancy significantly alters early post-partum breast milk fatty acid composition. omega-3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.

Chi-Square Distribution↗
PubMed2003

The value of perinatal immune responses in predicting allergic disease at 6 years of age.

BACKGROUND: Characterizing early abnormalities in immune development of allergic individuals provides an important basis for defining disease pathogenesis and future prevention strategies. This study compares patterns of early immune responses in an established cohort based on allergic outcomes and allergen skin prick test (SPT) reactions at 6 years of age. METHODS: Children from an original birth cohort (n = 60) consisting of 44 high risk (HR) (family history of allergy) and 16 low risk (LR) (no family history) were reassessed at 6 years of age. Detailed clinical information about allergic disease was obtained (n = 53) and a subgroup (n = 31) consented to have allergen SPT to common food and inhalant allergens. Data from previous immunological assessments performed at birth, 1 and 2 years of age, including lymphoproliferation and cytokine [interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13 and interferon (IFN)-gamma] responses to ovalbumin (OVA), house dust mite (HDM), cat allergen (Fel d 1), phytohaemaglutinin (PHA) and tetanus toxoid, were re-analysed based on the 6-year clinical outcomes. RESULTS: Twenty-eight HR and three LR children had a clinical history of allergic disease at 6 years of age including doctor diagnosed asthma (n = 17) and/or eczema (n = 24). Most children (78%) with atopy at 6 years had positive SPT to the allergens tested, and 70% had symptoms within the last year. Children at genetic risk (family history) of allergy had weaker (P = 0.017) polyclonal T helper 1 (Th1) IFN-gamma responses in the neonatal period compared with LR children. Although children with allergic disease at 6 years also tended to have weaker neonatal IFN-gamma responses compared to those with no symptoms, but this was not quite significant (P = 0.05). A positive SPT to HDM at 6 years was associated with higher IL-13 responses to HDM at 1 year (P = 0.02), whereas allergic disease at 6 years was associated with higher IL-5 messenger RNA (mRNA) responses to HDM at 1 year (P = 0.01). Despite these associations, regression analysis demonstrated that the only significant early predictors of allergic sensitization at 6 years of age were a family history of allergic disease, and atopic symptoms at 2 years. Importantly, none of the early immunological parameters measured were significantly predictive of allergic disease or allergic sensitization in these 6-year-olds. CONCLUSIONS: Although our observations suggest that subtle differential alterations in cytokine responses during early immune development are associated with different aspects of subsequent atopy, there are still no early predictive biomarkers of disease. A positive family history of allergy remains the dominant predictive factor.

Allergens↗
PubMed2003

Maternal smoking in pregnancy alters neonatal cytokine responses.

BACKGROUND: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood (CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus. METHODS: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ovalbumin (OVA) or house dust mite (HDM)] and mitogens [concanavalin A (ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy (n = 17) with responses of neonates whose mothers never smoked (n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme-linked immunosorbent assay [interleukin (IL)-13, IL-6, interferon (IFN)gamma and IL-10]. Cell pellets were also collected for cytokine mRNA detection (IL-5, IL-9, IFNgamma). RESULTS: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL-13 protein) responses to both HDM (P = 0.01) and OVA (P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL-9mRNA, IL-5mRNA and IL-6 responses, although these were not statistically significant. Although IFNgamma mRNA responses to PHA (P = 0.015) and ConA (P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNgamma protein responses to allergens or mitogens. CONCLUSIONS: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.

Adult↗
PubMed2003

Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy.

BACKGROUND AND OBJECTIVES: The epidemiological association between higher dietary n-3 polyunsaturated fatty acids (PUFA) and lower prevalence of asthma, has led to interest in the role of early dietary modification in allergic disease prevention. In this study we examined the effects of maternal n-3 (PUFA)-rich fish oil supplementation on cord blood (CB) IgE and cytokine levels in neonates at risk of developing allergic disease. METHODS: In a randomized double-blind, placebo-controlled trial, 83 atopic pregnant women received either fish oil capsules (n = 40) containing 3.7 g n-3 PUFA/day or placebo capsules (n = 43) from 20 weeks gestation until delivery. CB cytokine levels (IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, TNF-alpha and IFN-gamma) and total IgE levels were measured and compared between the two groups. Fatty acid composition of red cell membranes was analysed by gas chromatography and the relationships among PUFA, cytokine and IgE levels were examined. RESULTS: Maternal fish oil supplementation resulted in a significant increase in n-3 PUFA levels (P < 0.001) in neonatal erythrocyte membranes. Neonates whose mothers had fish oil supplementation had significantly lower plasma IL-13 (P < 0.05) compared to the control group. There was also a significant inverse relationship between levels of n-3 PUFA in neonatal cell membranes and plasma IL-13. There was no difference in levels of IgE and the other cytokines measured. CONCLUSIONS: This study provides preliminary evidence that increasing neonatal n-3 PUFA levels with maternal dietary supplementation can achieve subtle modification of neonatal cytokine levels. Further assessment of immune function and clinical follow-up of these infants will help determine if there are any significant effects on postnatal immune development and expression of allergic disease.

Double-Blind Method↗
PubMed2003

Neonatal interleukin-12 capacity is associated with variations in allergen-specific immune responses in the neonatal and postnatal periods.

BACKGROUND AND OBJECTIVES: A reduced capacity of antigen presenting cells (APC) to provide pro-T helper 1 (Th1) signals, such as IL-12, to T cells during early life may be implicated in the development of T helper 2 (Th2)-mediated allergic disease. In this study we examined the relationships between the capacity for IL-12 responses in the neonatal period and atopic risk (family allergy), in vitro T cell responses to allergens, and the subsequent development of allergic disease at 6 years. METHODS: The capacity of circulating neonatal (and maternal) APC to produce IL-12 p70 in response to LPS (and IFN-gamma) stimulation was assessed in a group of 60 children with previously well-characterized immune responses to allergens and atopic outcomes. The IL-12 responses were compared with allergen-induced lymphoproliferation (to house dust mite (HDM) ovalbumin (OVA), cat and beta-lactoglobulin (BLG)) and IL-13 and IFN-gamma cytokine responses (to OVA, HDM and phytohaemaglutinin (PHA)) in the neonatal and postnatal periods. IL-12 responses were also compared according to atopic risk and atopic outcomes (doctor-diagnosed asthma, eczema, food allergies and sensitization as evidenced by skin prick testing) at 6 years clinical follow-up. RESULTS: Maternal peripheral blood mononuclear cells (PBMC) synthesized significantly greater amounts of IL-12 than neonatal PBMC, though within maternal-infant pairs IL-12 responses were significantly correlated (r = 0.4, P = 0.019). Moreover, neonatal IL-12 responses were positively correlated with neonatal allergen proliferation for HDM (r = 0.6, P < 0.0001), OVA (r = 0.55, P < 0.0001), cat (r = 0.5, P = 0.003) and BLG (r = 0.55, P = 0.001), but negatively correlated with neonatal IL-13 responses to both allergens tested (HDM: r = - 0.4, P = 0.03 and OVA: r = - 0.5, P = 0.001). Both neonatal and maternal IL-12 responses were positively correlated with postnatal IFN-gamma responses to HDM at 12, 18 and 24 months of age (responses after age of 2 years were not assessed). There was no relationship between atopic risk and IL-12 capacity in the neonatal period, but there was a (non-significant) trend for neonatal IL-12 responses to be lower in the high-risk children who developed clinical allergy at 6 years (compared with the low risk group) although the number in this analysis was small. CONCLUSIONS: Reduced APC IL-12 production in the perinatal period was associated with reduced T cell activation (lymphoproliferation), stronger neonatal Th2 responses, and weaker Th1 responses to allergen in the postnatal period. This supports the notion that variations in APC function in early life may contribute to altered allergen-specific cytokine responses associated with later allergy.

Allergens↗
PubMed2003

New concepts of cytokines in asthma: is the Th2/Th1 paradigm out the window?

Although asthma is clearly associated with a systemic propensity for allergic T helper type 2 (Th2) cell cytokine responses, independent local immune events appear to be responsible for the development of allergic airways inflammation. There is growing interest in how local immune networks interact with resident airway cell populations such as epithelial cells, which are now also recognized as key producers of cytokines, chemokines and growth factors. As well as their recognized role in airway remodelling, epithelial cells are now thought to have a role in initiating events. This review examines the role of cytokines produced by these and other cells in the development of asthma. It also highlights emerging concepts that the excessive and inappropriate immune responses seen in allergic disease may be related to dysfunction of various interleukin-10 producing regulatory cell populations.

Asthma↗
PubMed2002

Cellular immune responses to ovalbumin and house dust mite in egg-allergic children.

BACKGROUND: Although IgE-mediated food (egg) allergy is typically lost with age the underlying immune mechanisms are not understood, particularly in relation to the development of persistent IgE-mediated aeroallergen sensitivity. METHODS: Lymphoproliferation and cytokine responses (IL-5, IL-10, IL-13 and IFN-gamma) to house dust mite (HDM) allergen and egg ovalbumin (OVA) were assessed using peripheral blood mononuclear cells (PBMC) from children aged 6 months to 5 years (n = 59) with acute IgE-mediated egg allergy (urticaria and angiedema or anaphylaxis), as confirmed by positive skin prick testing (SPT). Of these 46 had positive SPT on the day of blood collection and 13 had outgrown egg allergy (negative SPT and successful egg challenge). Where possible, responses were compared with previous data from nonallergic children of similar ages (n = 107). RESULTS: Transient lymphoproliferative responses to OVA were seen in both egg-allergic and nonallergic children, but were more marked and more prolonged in egg-allergic children. Younger egg-allergic children (< 18 months) showed a mixed Th0 cytokine response to OVA, with readily detectable IFN-gamma, IL-5, IL-13 IL-10. Although IL-13 and IL-5 responses (OVA) correlated in younger egg-allergic children, there was a dissociation of these Th2 responses with age. Loss of clinical reactivity to egg was associated with almost complete loss of IL-5 responses and OVA-specific lymphoproliferation. Although IL-13 levels tended to be lower with age, this was not significant. Strong IFN-gamma and IL-10 responses to OVA persisted in older children after loss of OVA-specific lymphoproliferation. Lymphoproliferative responses to HDM also developed earlier in egg-allergic children compared with nonallergic children. Th1 (IFN-gamma) responses to HDM were largely below detection prior to 18 months of age, but increased significantly with age. In egg-allergic children Th2 (IL-5, IL-13) HDM responses also progressively increased with age. At 3 years of age almost all egg-allergic children had positive SPT to HDM and positive lymphoproliferative responses to HDM, with strong Th1 and Th2 (Th0) cytokine production. CONCLUSIONS: IL-5 responses (rather than IL-13) responses most closely reflected clinical food allergy, with dissociation of IL-5 and IL-13 responses in older and egg-tolerant children. In this population, food and aeroallergen sensitivity was not associated with inability to produce IFN-gamma, but rather with mixed Th2 and Th1 (Th0) responses. Strong IL-10 and IFN-gamma responses where associated with the development of tolerance, suggesting persistent 'regulatory' populations of OVA-specific T cells, rather than clonal deletion of OVA responsive T-cells.

Animals↗
PubMed2000

Effects of maternal allergen-specific IgG in cord blood on early postnatal development of allergen-specific T-cell immunity.

BACKGROUND: A wide body of epidemiologic evidence indicates that as yet unknown maternal factor(s) can influence susceptibility to allergic disease in the offspring. It is also well established that the induction of allergen-specific T-cell memory is frequently initiated in utero, and it is likely that maternal factors exert their influence during this period. METHODS: This study examines the relationship between maternally derived allergen-specific IgG subclass antibodies and cellular immune responses (lymphoproliferation and cytokine production) against the same allergens in 49 subjects tested at birth and at 2 years of age. Polyclonal production of the Th1 cytokine IFN-gamma was also examined in the cord-blood samples. RESULTS: At birth, there were positive correlations between both house-dust mite (HDM)- and ovalbumin (OVA)-specific IgG subclass levels in cord blood, maternal atopy, and the magnitude of perinatal lymphoproliferative responses to respective allergens. Inverse relationships were also observed between cord-blood IgG antibody titres and allergen-specific production of some Th2 cytokines. However, there were no consistent relationships between cord-blood allergen-specific IgG antibodies and subsequent immune responses to allergens when the same subjects were retested at 2 years of age. An inverse relationship was observed between maternal history of atopy and perinatal IFN-gamma production capacity. CONCLUSIONS: Our results suggest that transplacental transfer of allergen-specific IgG antibody is unlikely to be a major mechanism for maternal regulation of allergen-specific immunity in infancy. An alternative possibility is that maternal effects may operate by influencing IFN-gamma production by T cells in the offspring.

Allergens↗
PubMed2000

Primary sensitization to inhalant allergens.

The neonatal T-cell system is capable of responding to allergens at birth, indicating the occurrence of prenatal sensitization, and the cytokine profile of these responses is skewed towards the Th-2 type. This response is further modified by postnatal exposure to different types of allergens. In relation to inhalant allergen (employed by HDM) the low level fetal Th-2 responses in non-atopics appear to be down-regulated rapidly after birth, parallel to an increase in allergen-specific IFN-gamma production. In contrast, atopics appear to consolidate their initial Th-2 responses, and around the age of 6 exhibit a cytokine response profile similar to the adult pattern. A pre-existing deficiency in IFN-gamma production may be one of the key factors determining the postnatal persistence of Th-2 responses in atopics.

Allergens↗
PubMed1999

Development of allergen-specific T-cell memory in atopic and normal children.

BACKGROUND: In the past 20-30 years, there has been an increase in prevalence of allergic respiratory diseases, particularly amongst children. This study is a prospective analysis of the postnatal maturation of T-helper cell (Th) responses to aeroallergens in atopic and non-atopic infants. METHODS: We measured mononuclear-cell proliferative and cytokine responses to specific allergens and tetanus toxoid in blood samples from atopic and non-atopic infants every 6 months from birth to 2 years of age. Cytokine analyses of responses to housedust-mite allergen used ELISA and reverse-transcriptase PCR. We also measured responses to Fel d1 (cat allergen) and tetanus toxoid. FINDINGS: Samples from 18 atopic and 13 non-atopic infants showed low-level Th2-skewed allergen-specific responses at birth, with little accompanying specific interferon-gamma production. Neonatal Th2 responses were lower in the atopic group than in the non-atopic group; the differences were significant for interleukin-4 (mRNA: beta-actin ratio 0.48 [SE 0.15] vs 0.15 [0.06], p=0.049), interleukin-6 (4750 [48] vs 1352 [51] pg/mL culture fluid, p=0.003), interleukin-10 (1162 [228] vs 485 [89], p=0.015), and interleukin-13 (7.1 [0.9] vs 0.9 [0.3], p=0.008). There was rapid suppression of Th2 responses during the first year of life in non-atopic children, but there was consolidation of responses in atopic children, associated with defective neonatal interferon-gamma production. INTERPRETATION: The continuation of fetal allergen-specific Th2 responses during infancy is a defining feature of the inductive phase of atopic disease, and is associated with decreased capacity for production of the Th1 cytokine interferon y by atopic neonates. These findings provide a plausible mechanism for persistence of the fetal Th2 responses during early childhood in atopic individuals and subsequent expression of disease.

Allergens↗
PubMed1999

Microbial stimulation as an aetiologic factor in atopic disease.

Epidemiologic evidence from various sources suggests that exposure to microbial stimuli during early childhood can influence the induction and expression of atopic diseases, particularly in the respiratory tract. Moreover, these effects may have long-lasting consequences in relation to expression of the atopic phenotype in adulthood. This review discusses key aspects of this evidence in relation to the underlying mechanisms which regulate T-helper (Th)-cell function; in particular, the generation of Th-memory cells responsive to inhalant allergens.

Adjuvants, Immunologic↗
PubMed1998

Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile.

The expression of Th2-skewed immunity against soluble protein Ags present in the normal environment is recognized as the primary cause of allergic inflammation in atopics. In contrast, nonallergic normal individuals display low level Th1-skewed immunity against the same Ags ("allergens"), which is perceived as conferring protection against Th2-dependent allergic sensitization. The type of T cell memory that develops against these Ags is currently believed to be the result of complex interactions between environmental and genetic susceptibility factors, which occur postnatally when the naive immune system directly confronts the outside environment. The results of the present study challenge this general concept. We demonstrate here for the first time that Th2-skewed responses to common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are present in virtually all newborn infants and are dominated by high level production of IL-10. Moreover, these responses are demonstrable within 24 h of culture initiation, arguing against a significant contribution from covert in vitro T cell priming and/or differentiation. These findings imply that the key etiologic factor in atopic disease may not be the initial acquisition of allergen-specific Th2-skewed immunity per se, but instead may be the efficiency of immune deviation mechanisms, which in normal (nonatopic) individuals redirect these fetal immune responses toward the Th1 cytokine phenotype.

Allergens↗