The regulatory effects of pyridoxine deficiency on the grass carp (Ctenopharyngodon idella) gill barriers immunity, apoptosis, antioxidant, and tight junction challenged with Flavobacterium columnar.

The effects of dietary pyridoxine (PN) on the gill immunity, apoptosis, antioxidant and tight junction of grass cap (Ctenopharyngodon idella) were investigated in this study. Fish were fed semi-purified diets containing graded levels of PN for 10 weeks, and then challenged with Flavobacterium columnare by bath immersion exposure for 3 days. The results indicated that compared with the optimal PN level, PN deficiency resulted in a decline in the antimicrobial compound production of gill. In addition, PN deficiency up-regulated the pro-inflammatory cytokines and down-regulated the anti-inflammatory cytokines gene expression, which might be associated with the enhanced nuclear factor κB p65 and the inhibited target of rapamycin signalling pathways, respectively, suggesting that PN deficiency could impair gill immune barrier function. Furthermore, PN deficiency (1) induced cell apoptosis, which may be partly associated with the (apoptotic protease activating factor-1, Bcl-2 associated X protein)/caspase-9 and c-Rel/tumor necrosis factor α (rather than FasL)/caspase-8 mediated apoptosis pathway. (2) Inhibited Kelch-like ECH-associating protein 1a/NF-E2-related factor 2 mRNA expression, decreased the mRNA expression and activities of antioxidant enzymes, increased the levels of reactive oxygen species, protein carbonyl and malondialdehyde. (3) Increased the mRNA expression level of myosin light chain kinase, which may be result in the down-regulation of tight junction complexes such as zonula occludens 1, occludin and claudins (expect claudin-12 and claudin-15). These results suggest that PN deficiency could impair gill physical barrier function. In summary, dietary PN deficiency could cause the impairment of gill barrier function associated with immunity, apoptosis, antioxidant and tight junction, which may result in the increased the susceptibility of fish to pathogenic bacteria. Moreover, based on the gill rot morbidity, LZ activity and MDA content, the dietary PN requirements for grass cap were estimated to be 4.85, 4.78 and 4.77 mg kg-1 diet, respectively.

Association of common variable immunodeficiency with vitamin B6 deficiency.

OBJECTIVE: To study the prevalence of vitamin B(6) deficiency in common variable immunodeficiency and the impact of vitamin B(6) supplementation on immune function in the disorder. DESIGN: Open, non-blinded. SETTING: Medical School Hannover, Hannover, Germany. SUBJECTS: Plasma vitamin B(6) concentrations were measured in all the 54 common variable immunodeficiency (CVID) patients visiting our outpatients' clinics in 2005. INTERVENTIONS: The 17 patients with a decreased vitamin B(6) concentration were recommended to take 50 mg of vitamin B(6)/day for 3 months. Then, vitamin B(6) concentrations, absolute number of lymphocyte populations and immunoglobulin concentrations were controlled. RESULTS: Vitamin B(6) concentrations were reduced in 17/54 patients. All 11/17 patients following our advice to substitute vitamin B(6) had normal vitamin B(6) plasma concentrations 3 months later. In parallel, the number of CD4(+) T cells significantly increased. In contrast, concentrations of serum immunoglobulins were not improved. CONCLUSIONS: Vitamin B(6) deficiency is common in CVID. The vitamin deficiency is not the cause of CVID and vitamin supplementation does not relieve humoral immunodeficiency. Nevertheless, vitamin B(6) should be measured in CVID to avoid possible long-term complications of its deficiency.

Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations.

The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

Pyridoxal-5'-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients.

BACKGROUND & AIMS: Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of pyridoxal-5'-phosphate decreasing their body reserves. This study was designed to assess the nutritional pyridoxal-5'-phosphate status in critical care patients with systemic inflammatory response syndrome, comparing them with a group of healthy people, and studying it's association with factors involved in the pyridoxine and other B vitamins metabolism, as the total antioxidant capacity and Hcy as cardiovascular risk biomarker. METHODS: Prospective, multicentre, comparative, observational and analytic study. One hundred and three critically ill patients from different hospitals, and eighty four healthy subjects from Granada, Spain, all with informed consent. Data from daily nutritional assessment, ICU severity scores, clinical and nutritional parameters, antioxidant status and homocysteine levels was taken at admission and at the seventh day of the ICU stay. RESULTS: Thiamine, riboflavin, pyridoxine and folate status proved deficient in a large number of patients, being significantly lower in comparison with control group, and significantly decreased at 7th day of ICU stay. Higher homocysteine was observed in patients compared with control group (p < 0.05) where 31.5 and 26.8 percent of subjects presented hyperhomocysteinemia at initial and final of study, respectively. Antioxidant status was lower than control group in two periods analysed, and decreased at 7th day of ICU stay (p < 0.05) being associated with PLP deficiency. PLP deficiency was also correlated with hyperhomocysteinemia at two times measured (r. -0.73, p < 0.001; r. -0.69, p < 0.001, respectively), showing at day 7 an odds ratio of 6.62 in our multivariate model. CONCLUSION: Critically ill patients with SIRS show deficient B vitamin and low antioxidant statuses. Despite association found between PLP deficiency and low antioxidant status in critically ill patients, PLP deficiency was only associated with hyperhomocysteinemia regardless of antioxidant, riboflavin, cobalamine, and folate statuses in critically ill patients with SIRS at seventh day of ICU stay. PLP deficient patients presented about six times more risk of cardiovascular disease than non deficients.

Plasma pyridoxal 5'-phosphate is a significant indicator of immune responses in the mechanically ventilated critically ill.

OBJECTIVES: This study assessed the effect of vitamin B6 status on immune responses in mechanically ventilated, critically ill patients and compared the results with those of healthy controls. METHODS: This was designed as a cross-sectional observational study. Forty patients in the intensive care unit successfully completed this study. Vitamin B6 intake was recorded for 8 d. Severity of illness (Second Acute Physiology and Chronic Health Evaluation score) was recorded. Thirty-eighty healthy controls were recruited from the physical check unit of Taichung Veterans General Hospital (Taichung, Taiwan). All control subjects were given instruction on how to complete a 24-d diet recall. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate [PLP] and 4-pyridoxic acid) and indirect measures (erythrocyte alanine and aspartate aminotransferase activity coefficients). Levels of serum albumin, hemoglobin, hematocrit, high-sensitivity C-reactive protein, and immune responses (white blood cell, neutrophil, total lymphocytes, T lymphocytes [CD3], B lymphocytes [CD19], T-helper cells [CD4], and suppressor cells [CD8]) were determined. RESULTS: Critically ill patients had sufficient vitamin B6 intake but showed marginal PLP deficiency (20.9 +/- 1.5 nmol/L). In addition, critically ill patients had significantly lower and abnormal immune responses than did healthy controls. There was no significant correlation of vitamin B6 intake and erythrocyte alanine and aspartate aminotransaminase activity coefficients with immune indices. Plasma PLP concentration was strongly negatively correlated with high-sensitivity C-reactive protein level. However, plasma PLP was significantly associated with immune responses after adjustment for age, sex, high-sensitivity C-reactive protein, and the other four vitamin B6 indicators. CONCLUSIONS: Plasma PLP is a significant indicator of immune responses in human subjects. Further research is warranted to study whether vitamin B6 supplementation in critically ill patients improves their immune responses.

Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults.

The effect of vitamin B-6 deficiency on immune response was studied in eight healthy elderly adults. The protocol consisted of a 5-d baseline (BL) period; a vitamin B-6-depletion period of less than or equal to 20 d; three stages of vitamin B-6-repletion, each lasting 21 d; and a 4-d final phase. The amounts of vitamin B-6 ingested during the different phases of the study were 3.00, 15.00, 22.50, and 33.75 micrograms.kg body wt-1.d-1, respectively. During the final phase the subjects ingested 50 mg vitamin B-6/d. Fasting blood was collected at the end of each period. Vitamin B-6 depletion significantly decreased percentage and total number of lymphocytes, mitogenic responses of peripheral blood lymphocytes to T- and B-cell mitogens, and interleukin 2 production. These indices returned to BL values after the third vitamin B-6-repletion period, when the total vitamin B-6 intakes were 1.90 +/- 0.18 mg/d for women and 2.88 +/- 0.17 mg/d for men. Vitamin B-6 deficiency impairs in vitro indices of cell-mediated immunity in healthy elderly adults. This impairment is reversible by vitamin B-6 repletion.

Association of vitamin B6 status with parameters of immune function in early HIV-1 infection.

Nutritional deficiencies have been documented to affect immune function. The present study indicates that vitamin B6 deficiency is prevalent in CDC stage III HIV-1-infected subjects, despite adequate dietary vitamin B6 intake. As vitamin B6 deficiency has been previously shown to affect immune function, these relatively asymptomatic HIV-1-infected patients were examined for evidence of a relationship between vitamin B6 deficiency and immune dysregulation. Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity [multivariate F(3,36) = 3.70, p less than or equal to 0.02]. Additional analyses indicated that overtly deficient participants exhibited significantly decreased lymphocyte responsiveness to the mitogens phytohemagglutinin and pokeweed, and reduced natural killer cell cytotoxicity, compared to subjects with clearly adequate vitamin B6 status (chi 2 = 8.78, df = 3, p less than 0.04). Vitamin B6 status was not related to immune cell subpopulations, e.g., CD4, CD8 cell number, or level of serum immunoglobulins. The results of this study indicate that while vitamin B6 status is not a primary etiological factor in HIV-1-related immunological dysregulation, it appears to be an important cofactor of immune function.

Vitamin B6 and immune competence.

Animal and human studies suggest that vitamin B6 deficiency affects both humoral and cell-mediated immune responses. Lymphocyte differentiation and maturation are altered by deficiency, delayed-type hypersensitivity responses are reduced, and antibody production may be indirectly impaired. Although repletion of the vitamin restores these functions, megadoses do not produce benefits beyond those observed with moderate supplementation. Additional human studies indicate that vitamin B6 status may influence tumor growth and disease processes. Deficiency of the vitamin has been associated with immunological changes observed in the elderly, persons infected with human immunodeficiency virus (HIV), and those with uremia or rheumatoid arthritis. Future research efforts should focus on establishing the mechanism underlying the effects of vitamin B6 on immunity and should attempt to establish safe intake levels that optimize immune response.

Vitamin B6 and immune function in the elderly and HIV-seropositive subjects.

Vitamin B6 plays an important role in immune response. A recent investigation of healthy elderly subjects in a vitamin B6 depletion-repletion study indicates that B6 deficiency impairs interleukin-2 production and lymphocyte proliferation. Another study in HIV-1-infected patients found impaired immune responsiveness in patients with compromised vitamin B6 status.

Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjögren's syndrome.

BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjögren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

Effects of the colour additive caramel colour III on the immune system: a study with human volunteers.

Administration of the colour additive Caramel Colour III to rats has been associated with decreased numbers of lymphocytes and several other changes in the immune system, as well as in immune function parameters, specifically in animals fed a diet with a relatively low vitamin B6 content. The effects are caused by the imidazole derivative 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). Caramel Colour III is commonly used in food products such as bakery products, soya-bean sauces, brown sauces, gravies, soup aromas, brown (dehydrated) soups, brown malt caramel blend for various applications, vinegars and beers, and effects in humans on dietary intake cannot be excluded. Elderly male volunteers with a marginal deficit in vitamin B6 were considered a relevant and potentially sensitive group to study possible effects of Caramel Colour III on blood lymphocyte numbers (total and within subsets) or on proliferative responses of lymphocytes to mitogenic stimulation. In addition, several other haematological parameters, as well as serum immunoglobulin levels and immunoglobulin production in vitro by pokeweed mitogen-stimulated mononuclear blood cells were studied. The results of this double-blind intervention study demonstrated that in a selected test group of apparently healthy elderly male volunteers with a biochemically marginally deficient vitamin B6 status, Caramel Colour III containing 23 (commercial sample) or 143 (research sample) ppm THI and administered at the level of the current acceptable daily intake of 200 mg/kg body weight/day for 7 days did not affect any of the factors investigated.

Role of the B vitamins in the immune response.

Studies conducted in our laboratory relating to the development of immune processes in B vitamin deficiency states of experimental animals have been reviewed. 1. The significant participation of certain of these nutritional factors in the production of circulating antibodies to a variety of antigens and the manifestation of delayed hypersensitivity reactions, including the rejection of tissue transplants, have been described. 2. Investigations on the mode of action of pyridoxine and pantothenic acid have demonstrated a marked reduction in the production of antibody-forming cells following antigenic stimulation in both deficiency states. The metabolism of antigen appeared to be normal. However, these two vitamins seem to function at different loci in the development of the immune process. Whereas pyridoxine appears to be necessary for the production of "C1" units from serine which are required for the biosynthesis of nucleic acids, it seems likely that pantothenic acid is involved in the secretion of newly-synthesized proteins into the extracellular compartment.

Effect of dietary vitamin B6 contents on antibody production.

When mice were placed on diets extreme deficient in vitamin B6, ovalbumin-dependent antibody productions (IgE, IgG1, IgG2a) were significantly suppressed, and alanine aminotransferase activity in the liver was also significantly decreased. In the case of pyridoxine excess (6 mg% = about ten times standard amount) in a 70% casein diet, ovalbumin-dependent antibody productions were also considerably suppressed. These responses were weaker in a low casein (5%) or normal casein (20%) diet than in a 70% casein diet. The administration of high doses of pyridoxine (6 mg%) resulted in the suppression of hepatic cathepsin B activity. Therefore, we conclude that ovalbumin-dependent antibody productions (IgG1, IgE) were suppressed by pyridoxine excess diet (6 mg%), because hepatic cathepsin B activity was suppressed by the excess pyridoxine in diet.

[Lysosomal hydrolase activity of the rat liver, spleen and thymus during antigenic stimulation and vitamin B6 deficiency]. / Aktivnost' lizosomal'nykh gidrolaz v pecheni, selezenke i timuse krys pri antigennoi stimuliatsii i defitsite vitamina B6.

Activity of cathepsins A, B, C and D and protein half-life T1/2 in rat liver, spleen and thymus tissues, content of antibody-producing cells in spleen, titer of antibodies and the complement activity were studied after antigen stimulation accompanied by vitamin B6 deficiency. Deficiency of vitamin B6 caused a distinct decrease in immune response and in activation of thiol-dependent proteinases in thymus, while the enzymatic activity was lowered in liver tissue. At the same time, the protein T1/2 was increased by 39% in liver tissue and decreased by 36% in thymus. These data suggest the importance of lysosomal thiol-dependent proteinases in immunogenesis.

[Biosynthesis of pyridoxal-5'-phosphate in lymphocytes stimulated by alloantigens in vitro]. / Biosintez piridoksal'-5'-fosfata v limfotsitakh, stimulirovannykh alloantigenami in vitro.

Dynamics of alterations in pyridoxal kinase activity (key enzyme in biosynthesis of pyridoxal-5'-phosphate) was studied in lymphocytes of mice BALB/c, stimulated by irradiated cells from spleen of mice C3H in vitro. The cytolytic activity of lymphocytes was estimated by amount of Na251CrO4 realised from lysed cell-targets into medium. Maintenance of animals on a diet without pyridoxine within 1-3 weeks did not affect on the capacity of lymphocytes to proliferative in vitro and on their cytolytic activity. At the same time pyridoxal kinase activity was increased 2.5-3-fold in stimulated lymphocytes in presence of pyridoxal. Km value was 2.5-5.0.10(-5) M of pyridoxal for preparations of pyridoxal kinase from lymphocytes either with normal or with increased enzymatic activity. Lymphocytes of mice, kept on the diet without pyridoxine within 5-6 weeks, were characterized by distinctly decreased proliferative and cytolytic activities. Pyridoxal-5'-phosphate, added to incubation mixture in vitro, as distinct from pyridoxal, restored partially the impaired functions of T-lymphocytes.