Selenium is found at the active centre of twenty-five selenoproteins which have a variety of roles, including the well-characterised function of antioxidant defense, but it also is claimed to be involved in the immune system. However, due to limited and conflicting data for different parameters of immune function, intakes of selenium that have an influence on immune function are uncertain. This review covers the relationship between selenium and immune function in man, focusing on the highest level of evidence, namely that generated by randomised controlled trials (RCT), in which the effect of selective administration of selenium, in foods or a supplement, on immune function was assessed. A total of nine RCT were identified from a systematic search of the literature, and some of these trials reported effects on T and natural killer cells, which were dependent on the dose and form of selenium administered, but little effect of selenium on humoral immunity. There is clearly a need to undertake dose–response analysis of cellular immunity data in order to derive quantitative relationships between selenium intake and measures of immune function. Overall, limited effects on immunity emerged from experimental studies in human subjects, though additional investigation on the potential influence of selenium status on cellular immunity appears to be warranted.

Post-transplantation lymphoproliferative disorder is a potentially mortal complication after heart transplantation in children. As the immune system plays a crucial role in the development of lymphoma, we explored the influence of thymus function in relation to immunosuppressive treatment in organ-transplanted children and healthy control subjects. A prospective case–control study was performed at a single centre, in which 36 children who had undergone heart transplantation were compared to two control groups: 34 kidney-transplanted children and 33 healthy age- and sex-matched children. T- and B-lymphocyte subtypes and monocytes were analysed by flow cytometry, and T-cell receptor excision circles were assessed using quantitative polymerase chain reaction. Heart-transplanted children had a lymphocyte profile characterised by reduced or absent thymic function with low numbers of T-cell receptor excision circles and total and naïve T cells, together with immune activation against the allograft. Despite similar immunosuppressive treatment, the kidney-transplanted group showed an activated T-lymphocyte compartment.

Enhancing the supply of arginine (Arg), a semi-essential amino acid, has positive effects on immune function in dairy cattle experiencing metabolic stress during early lactation. Our objective was to determine the effects of Arg supplementation on biomarkers of liver damage and inflammation in cows during early lactation. Six Chinese Holstein lactating cows with similar BW (508 ± 14 kg), body condition score (3.0), parity (4.0 ± 0), milk yield (30.6 ± 1.8 kg) and days in milk (20 ± days) were randomly assigned to three treatments in a replicated 3 × 3 Latin square design balanced for carryover effects. Each period was 21 days with 7 days for infusion and 14 days for washout. Treatments were (1) Control: saline; (2) Arg group: saline + 0.216 mol/day l-Arg; and (3) Alanine (Ala) group: saline + 0.868 mol/day l-Ala (iso-nitrogenous to the Arg group). Blood and milk samples from the experimental cows were collected on the last day of each infusion period and analyzed for indices of liver damage and inflammation, and the count and composition of somatic cells in milk. Compared with the Control, the infusion of Arg led to greater concentrations of total protein, immunoglobulin M and high density lipoprotein cholesterol coupled with lower concentrations of haptoglobin and tumor necrosis factor-α, and activity of aspartate aminotransferase in serum. Infusion of Ala had no effect on those biomarkers compared with the Control. Although milk somatic cell count was not affected, the concentration of granulocytes was lower in response to Arg infusion compared with the Control or Ala group. Overall, the biomarker analyses indicated that the supplementation of Arg via the jugular vein during early lactation alleviated inflammation and metabolic stress.

Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.

Concentrate inclusion levels in dairy cow diets are often adjusted so that the milk yield responses remain economic. While changes in concentrate level on performance is well known, their impact on other biological parameters, including immune function, is less well understood. The objective of this study was to evaluate the effect of concentrate inclusion level in a grass silage-based mixed ration on immune function. Following calving 63 (45 multiparous and 18 primiparous) Holstein Friesian dairy cows were allocated to one of three isonitrogenous diets for the first 70 days of lactation. Diets comprised of a mixture of concentrates and grass silage, with concentrates comprising either a low (30%, LC), medium (50%, MC) or high (70%, HC) proportion of the diet on a dry matter (DM) basis. Daily DM intakes, milk yields and BW were recorded, along with weekly body condition score, milk composition and vaginal mucus scores. Blood biochemistry was measured using a chemistry analyzer, neutrophil phagocytic and oxidative burst assessed using commercial kits and flow cytometry, and interferon-γ production evaluated by ELISA after whole blood stimulation. Over the study period cows on HC had a higher total DM intake, milk yield, fat yield, protein yield, fat+protein yield, protein content, mean BW and mean daily energy balance, and a lower BW loss than cows on MC, whose respective values were higher than cows on LC. Cows on HC and MC had a lower serum non-esterified fatty acid concentration than cows on LC (0.37, 0.37 and 0.50 mmol/l, respectively, P=0.005, SED=0.032), while cows on HC had a lower serum β-hydroxybutyrate concentration than cows on MC and LC (0.42, 0.55 and 0.55 mmol/l, respectively, P=0.002, SED=0.03). Concentrate inclusion level had no effect on vaginal mucus scores. At week 3 postpartum, cows on HC tended to have a higher percentage of oxidative burst positive neutrophils than cows on LC (43.2% and 35.3%, respectively, P=0.078, SED=3.11), although at all other times concentrate inclusion level in the total mixed ration had no effect on neutrophil phagocytic or oxidative burst characteristics, or on interferon-γ production by pokeweed mitogen stimulated whole blood culture. This study demonstrates that for high yielding Holstein Friesian cows managed on a grass silage-based diet, concentrate inclusion levels in early lactation affects performance but has no effect on neutrophil or lymphocyte immune parameters.

The objective of this study was to determine if a moderate or high reduction of dietary CP, supplemented with indispensable amino acids (IAA), would affect growth, intestinal morphology and immunological parameters of pigs. A total of 40 barrows (initial BW=13.50±0.50 kg, 45±2 day of age) were used in a completely randomized block design, and allocated to four dietary treatments containing CP levels at 20.00%, 17.16%, 15.30% and 13.90%, respectively. Industrial AA were added to meet the IAA requirements of pigs. After 4-week feeding, blood and tissue samples were obtained from pigs. The results showed that reducing dietary CP level decreased average daily gain, plasma urea nitrogen concentration and relative organ weights of liver and pancreas (P<0.01), and increased feed conversion ratio (P<0.01). Pigs fed the 13.90% CP diet had significantly lower growth performance than that of pigs fed higher CP at 20.00%, 17.16% or 15.30%. Moreover, reducing dietary CP level decreased villous height in duodenum (P<0.01) and crypt depth in duodenum, jejunum and ileum (P<0.01). The reduction in the dietary CP level increased plasma concentrations of methionine, alanine (P<0.01) and lysine (P<0.05), and decreased arginine (P<0.05). Intriguingly, reducing dietary CP level from 20.00% to 13.90% resulted in a significant decrease in plasma concentration of IgG (P<0.05), percentage of CD3+T cells of the peripheral blood (P<0.01), also down-regulated the mRNA abundance of innate immunity-related genes on toll-like receptor 4, myeloid differentiation factor 88 (P<0.01) and nuclear factor kappa B (P<0.05) in the ileum. These results indicate that reducing dietary CP level from 20.00% to 15.30%, supplemented with IAA, had no significant effect on growth performance and had a limited effect on immunological parameters. However, a further reduction of dietary CP level up to 13.90% would lead to poor growth performance and organ development, associated with the modifications of intestinal morphology and immune function.

This study was conducted to investigate the effect of in ovo feeding (IOF) of folic acid on the folate metabolism, immune function and the involved epigenetic modification of broilers. A total of 400 (Cobb) hatching eggs were randomly divided into four groups (0, 50, 100 and 150 µg injection of folic acid at embryonic age 11 d), and chicks hatched from each treatment were randomly divided into six replicates with 12 broilers/replicate after incubation. The results indicated that, in ovo, 100- and 150-µg folic acid injections improved the hatchability. The average daily gain and feed conversion ratio increased in the 150-µg group during the late growth stage. Simultaneously, in the 100- and 150-µg groups, an increase was observed in hepatic folate content and the expression of methylenetetrahydrofolate reductase (d1 and 42) and methionine synthase reductase (d21). IgG and IgM concentrations, as well as plasma lysozyme activity of broilers, showed a marked increase along with increasing folic acid levels. The splenic expression levels of IL-2 and IL-4 were up-regulated, whereas that of IL-6 was down-regulated, in the 100- and 150-µg folic acid treatment groups. In addition, histone methylation in IL-2 and IL-4 promoters exhibited an enrichment of H3K4m2 but a loss of H3K9me2 with the increased amount of folic acid additive. In contrast, a decrease in H3K4m2 and an increase in H3K9me2 were observed in the IL-6 promoter in folic acid treatments. Furthermore, in ovo, the 150-µg folic acid injection improved the chromatin tightness of the IL-2 and IL-4 promoter regions. Our findings suggest that IOF of 150 µg of folic acid can improve the growth performance and folate metabolism of broilers, and enhance the relationship between immune function and epigenetic regulation of immune genes, which are involved with the alterations in chromatin conformation and histone methylation in their promoters.

Plant sterols and stanols inhibit intestinal cholesterol absorption and consequently lower serum LDL-cholesterol (LDL-C) concentrations. The underlying mechanisms are not yet known. In vitro and animal studies have suggested that changes in intestinal sterol metabolism are attributed to the LDL-C-lowering effects of plant stanol esters. However, similar studies in human subjects are lacking. Therefore, we examined the effects of an acute intake of plant stanol esters on gene expression profiles of the upper small intestine in healthy volunteers. In a double-blind cross-over design, fourteen healthy subjects (eight female and six male; age 21–55 years), with a BMI ranging from 21 to 29 kg/m2, received in random order a shake with or without plant stanol esters (4 g). At 5 h after consumption of the shake, biopsies were taken from the duodenum (around the papilla of Vater) and from the jejunum (20 cm distal from the papilla of Vater). Microarray analysis showed that the expression profiles of genes involved in sterol metabolism were not altered. Surprisingly, the pathways involved in T-cell functions were down-regulated in the jejunum. Furthermore, immunohistochemical analysis showed that the number of CD3 (cluster of differentiation number 3), CD4 (cluster of differentiation number 4) and Foxp3+ (forkhead box P3-positive) cells was reduced in the plant stanol ester condition compared with the control condition, which is in line with the microarray data. The physiological and functional consequences of the plant stanol ester-induced reduction of intestinal T-cell-based immune activity in healthy subjects deserve further investigation.

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25–65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.

The immunomodulatory effects of live or non-viable lactic acid bacteria have been extensively investigated. We reported that oral intake of heat-killed Lactobacillus plantarum L-137 (HK L-137) augmented innate and acquired immunity in mice and human subjects. To examine the effects of HK L-137 intake on upper respiratory tract infection (URTI) symptoms and immune functions in human subjects, a randomised, double-blind, placebo-controlled, parallel study was conducted in subjects with high psychological stress levels. A total of seventy-eight healthy subjects (thirty-three men and forty-five women; mean age 50·6 years) with scores of >41 on eighteen-item subscales of psychological distress in the Brief Job Stress Questionnaire were randomly assigned to receive a tablet containing HK L-137 (10 mg) or a placebo tablet daily for 12 weeks. The URTI symptoms were rated once daily on the validated twenty-one-item Wisconsin Upper Respiratory Symptom Survey-21. Immune functions, such as concanavalin A-induced proliferation and percentages of interferon (IFN)-γ- and IL-4-producing CD4 T cells of peripheral blood mononuclear cells (PBMC), and serum IFN-β concentrations were measured every 4 weeks. URTI incidence was significantly lower in the HK L-137 group than in the control group. URTI incidence, duration and severity, and duration of medication showed significant negative correlations with duration of HK L-137 intake. The percentage change from baseline of concanavalin A-induced proliferation of PBMC was significantly greater in the HK L-137 group than in the control group. These findings suggest that daily HK L-137 intake can decrease URTI incidence in healthy subjects, possibly through augmentation of immune functions.

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being.

Intra-uterine growth-retarded (IUGR) neonates have shown an impairment of postnatal intestinal development and function. We hypothesised that the immune function of IUGR neonates might be affected by increased nutrient intake (NI) during the suckling period. Therefore, we investigated the effects of high NI (HNI) on the growth performance, intestinal morphology and immunological response of IUGR and normal-birth weight (NBW) piglets. A total of twelve pairs of IUGR and NBW piglets (7 d old) were randomly assigned to two different nutrient-level formula milk groups. After 21 d of rearing, growth performance, the composition of peripheral leucocytes, serum cytokines and intestinal innate immune-related genes involved in the Toll-like receptor (TLR)-4–myeloid differentiation factor 88–NF-κB pathway were determined. The results indicated that IUGR decreased the average daily DM intake (ADMI) and the average daily growth (ADG). However, the ADMI and ADG were increased by HNI, irrespective of body weight. Likewise, serum cytokines (TNF-α and IL-1β) and ileal gene expressions (TLR-4, TLR-9, TRAF-6 and IL-1β) were lower in IUGR piglets, whereas HNI significantly increased blood lymphocyte percentage and serum IL-10 concentrations, but decreased neutrophil percentage, serum IL-1β concentrations and ileal gene expressions (NF-κB and IL-1β). Furthermore, IUGR piglets with HNI exhibited lower serum concentrations of TNF-α and IL-1β than NBW piglets, and these alterations in the immune traits of IUGR piglets receiving HNI were accompanied by decreasing ileal gene expressions of TLR-4, TLR-9, NF-κB and IL-1β that are related to innate immunity. In conclusion, the present findings suggest that increased NI during the suckling period impaired the immune function of neonatal piglets with IUGR.

The present study was conducted to evaluate the immune-enhancing effects of dietary l-glutamine supplementation in porcine circovirus type 2 (PCV2)-infected mice, and to examine the clearance effects of glutamine against PCV2 in experimentally infected mice. A total of sixty Kunming female mice were infected with PCV2 at a dose of 100 TCID50 (50 % tissue culture infection dose) by intraperitoneal injection after 2 weeks of dietary l-glutamine supplementation or l-alanine supplementation (as the control (isonitrogenous) group). The measured variables on 3rd, 5th, 7th, 9th and 11th d post-infection (dpi) included: (1) PCV2 virus loaded in the liver, spleen, heart, lung, kidney, ovary and serum was determined by real-time PCR; (2) IL-2, IL-6, IL-10, interferon (IFN)-α, IFN-γ and C-reactive protein levels in serum were measured by ELISA; (3) serum total superoxide dismutase activity was measured spectrophotometrically at 550 nm absorbance. Dietary l-glutamine supplementation significantly increased serum IL-2 levels on the 3rd (P< 0·01), 5th (P< 0·01), 7th (P< 0·05) and 9th dpi, significantly (P< 0·05) increased serum IL-6 levels on 3rd dpi, significantly (P< 0·05) increased serum IFN-γ levels on the 9th and 11th dpi and significantly decreased (P< 0·01) serum IL-10 levels on the 9th and 11th dpi, compared with those in the control group. Meanwhile, the PCV2 virus genome was detected sporadically throughout the experimental period in both groups. Taken together, the present results suggest that dietary l-glutamine supplementation enhances immune function in PCV2-infected mice.

Deoxynivalenol (DON) is prevalent worldwide in crops used for food and feed production. The presence of mycotoxins in poultry feeds is a significant factor contributing to financial losses in animal industries. DON causes losses in livestock production and poses a health problem to livestock and humans consuming contaminated cereal products. Although DON is one of the least acutely toxic trichothecenes, it should be treated as an important food safety issue because it is a very common contaminant of grains. Poultry respond to increasing dietary DON concentrations with a reduction in productivity only at high levels (above 5 mg/kg) but there is no evidence of a clear dose-response relationship. Poultry fed low to moderate doses are able to recover from initial weight losses, while higher doses induce more long-term changes in feeding behaviour. At low dosages of DON, haematological, clinical and immunological changes are transitory and decrease as compensatory/adaptation mechanisms are established. The exposure to higher dose levels of DON are mainly expressed as severe reductions in body weight and impaired resistance to infection, particularly bacterial infection. Common symptoms of acute toxicity of DON are nausea, vomiting, dermal irritation and lesions, haemorrhagic lesions and pathological changes in the haemopoietic organs.

The capacity of DON to alter normal gut and immune function has been of particular interest. One important aspect of DON toxicity is an injury of the gastrointestinal tract. It was found that DON had an influence on intestinal nutrient absorption and the intestinal morphology of chickens, especially in the duodenum and jejunum, as evidenced by shorter and thinner villi. DON decreases glucose and amino acid absorption in the chicken's small intestine in vivo and in vitro and this effect is apparently mediated by the inhibition of the sodium D-glucose co-transporter. It was found that immune function decreased in broiler Leghorn chicks that were fed DON-contaminated diets. It induces changes in the hematopoietic system of chicks and alters immune response, whereas, DON impairs mitogen-induced proliferation of lymphocytes. The feeding of DON-contaminated grains decreased serum antibody titers against Newcastle disease virus (NDV) and infectious bronchitis (IB) in laying hens and broilers. The impact of DON on the immune system and gastrointestinal tract are important to define the maximum tolerable levels of DON in animal feedstuffs. The purpose of this review is to summarise the information to date regarding the toxicological and immunological effects of DON on poultry.

Previously, we showed that mice fed white button mushrooms (WBM) had enhanced immune functions known to help the body's antiviral defence. In the present study, we tested whether WBM conferred protection against viral infection. Young (4-month-old) and old (22-month-old) C57BL/6 mice were fed a diet containing 0, 2 or 10 % WBM powder for 8 weeks. Mice were then infected with influenza Puerto Rico/8/34 (H1N1), and killed at day 0 (uninfected), 2, 5 or 7 post-infection. The primary outcomes of the study were viral titre and body weight. Secondary outcomes were natural killer (NK) cell activity, lymphocyte proliferation and cytokine production. The results showed that WBM did not affect viral titre, nor did it prevent infection-induced weight loss. WBM supplementation was found to enhance NK cell activity in old mice and to increase interferon (IFN)-γ production in young and old mice under naive (uninfected) conditions, but it had no such effect after infection. The lack of a mushroom supplementation effect on NK activity and concanavalin A-stimulated IFN-γ production after infection may explain the immune system's failure to reduce viral load and weight loss in mice after influenza infection. WBM supplementation, however, did induce changes in other aspects of the immune response: it significantly increased the production of T-helper type 2 cytokines IL-4 and IL-10 in uninfected mice and pro-inflammatory cytokines IL-1β and TNF-α in infected mice. These mushroom-induced systemic changes, however, were not adequate to confer a protective effect against influenza infection.

The present report summarises key insights from a recent symposium focusing on the impact of the intestinal microbiota on health and disease. A more appropriate definition of health was proposed since health maintenance is a dynamic process better assessed in terms of ability to adapt to stress and maintain physiological homeostasis. Biomarkers specifically for health are needed; use of challenge models and subjects with suboptimal health or specific disease risk were advised. The complexity of interactions between external factors, the intestinal epithelium, intestinal microbiota, the immune system and health was exemplified by describing the effects of antibiotics, the Western diet and non-digestible carbohydrates on the microbiota. The association of certain bacteria with different states of health or disease was acknowledged but also that is not always clear whether this is a cause or effect. Recent identification of three robust faecal metagenome clusters may advance this understanding. It was speculated that knowledge of the intestinal microbiota profile may eventually help in the diagnosis of health risks and choice of therapy. It was agreed that beneficial manipulation of the commensal microbiota can improve health outcome. For this purpose, three areas were reviewed. Firstly, research into probiotics as vaccine adjuvants was considered useful for substantiation of immune function claims. Secondly, positive results with certain probiotics and synbiotics for colorectal cancer are emerging, mostly from in vitro and animal studies. Finally, studies in endurance athletes have shown strain-specific probiotic benefit in terms of maintenance of immune function and, for certain strains, reduction of episodes of respiratory and/or gastrointestinal tract infections.

β2-1 fructans are considered to be prebiotics. Current literature indicates that β2-1 fructans may modulate some aspects of immune function, improve the host's ability to respond to certain intestinal infections, and modify some inflammatory outcomes in human subjects. However, there is a need to find out more about the modulation of immune markers by β2-1 fructans in humans. Healthy human subjects aged 45–65 years were randomly allocated to β2-1 fructans (Orafti® Synergy1; 8 g/d; n 22) or the digestible carbohydrate maltodextrin as placebo (n 21) for 4 weeks. Blood, saliva and faecal samples were collected at study entry and after 4 weeks. Immune parameters were measured using the blood and saliva samples and bifidobacteria were measured in the faecal samples. Faecal bifidobacteria numbers increased in the Orafti® Synergy1 group (P < 0·001) and were different at 4 weeks from numbers in the placebo group (P = 0·001). There was no significant effect of Orafti® Synergy1 on any of the immune parameters measured (blood immune cell subsets, total serum Ig, salivary IgA, neutrophil and monocyte phagocytosis of Escherichia coli and respiratory burst in response to E. coli or phorbol ester, natural killer cell activity, T cell activation and proliferation, production of six cytokines by T cells). It is concluded that, compared with maltodextrin, Orafti® Synergy1 has a bifidogenic effect in healthy middle-aged human subjects but does not alter immune responses examined in the absence of an in vivo immune challenge.

There is considerable interest in the strain specificity of immune modulation by probiotics. The present study compared the immunomodulatory properties of six probiotic strains of different species and two genera in a human peripheral blood mononuclear cell (PBMC) model in vitro. Live cells of lactobacilli (Lactobacillus casei Shirota, L. rhamnosus GG, L. plantarum NCIMB 8826 and L. reuteri NCIMB 11951) and bifidobacteria (Bifidobacterium longum SP 07/3 and B. bifidum MF 20/5) were individually incubated with PBMC from seven healthy subjects for 24 h. Probiotic strains increased the proportion of CD69+ on lymphocytes, T cells, T cell subsets and natural killer (NK) cells, and increased the proportion of CD25+, mainly on lymphocytes and NK cells. The effects on activation marker expression did not appear to be strain specific. NK cell activity was significantly increased by all six strains, without any significant difference between strains. Probiotic strains increased production of IL-1β, IL-6, IL-10, TNF-α, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein 1α to different extents, but had no effect on the production of IL-2, IL-4, IL-5 or TNF-β. The cytokines that showed strain-specific modulation included IL-10, interferon-γ, TNF-α, IL-12p70, IL-6 and monocyte chemotactic protein-1. The Lactobacillus strains tended to promote T helper 1 cytokines, whereas bifidobacterial strains tended to produce a more anti-inflammatory profile. The results suggest that there was limited evidence of strain-specific effects of probiotics with respect to T cell and NK cell activation or NK cell activity, whereas production of some cytokines was differentially influenced by probiotic strains.