Immunomodulatory Effect of a Salvia plebeia R. Aqueous Extract in Forced Swimming Exercise-induced Mice.

This study investigated the immunomodulatory effect of Salvia plebeia R. aqueous extract (FIE-SP, SPW) in forced swimming exercise-induced mice and the immunostimulatory effects on Raw264.7 cells. Mice were randomly assigned to four groups: the control group (CON), the forced swimming test group (FST), and two FIE-SP groups (low and high dose of FIE-SP). Compared with the control group, the FIE-SP groups showed significantly increased ratios of T lymphocyte surface markers CD4+/CD8+ and major histocompatibility complex (MHC)I/MHCII, as well as increased concentrations of immunoglobulin (Ig)A and IgG. FIE-SP groups significantly increased Th1 cytokines and decreased Th2 cytokines compared with negative control exercise-induced mice. Conversely, the immunostimulatory effects of FIE-SP significantly increased phagocytic activities, nitric oxide (NO) production, and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß in Raw264.7 cells. Furthermore, FIE-SP increased natural killer (NK) cell activities and cytokines (IL-12) in splenocytes compared with the CON group. These results indicated that FIE-SP supplementation could prevent imbalanced immune states and produce immunostimulatory effects to support innate immunity.

Effect of zinc supplementation on mycospecific immunoglobulins in tuberculosis patients.

The effect of zinc supplementation on the serum level of IgA, IgG, IgM mycospecific immunoglobulins in tuberculosis patients alongwith normal control and disease control subjects were studied. It was observed that with antituberculous drugs for one month (without zinc supplementation), the serum level of immunoglobulins in tuberculosis subjects although decreased significantly, but with zinc supplementation along with antituberculous drugs for one month the decrease in the level of immunoglobulins in serum was more significant. This may be attributed to the effect of zinc supplementation favouring the normal compartmentalisation state of iron and also to the immunomodulatory effect of zinc.

Effects of early enteral nutrition supplemented with arginine on intestinal mucosal immunity in severely burned mice.

BACKGROUND: To investigate the effects of early enteral nutrition (EN) supplemented with Arginine (Arg) on intestinal mucosal immunity in severely burned mice. METHODS: Forty-four mice were randomly assigned into four groups: a sham injury+EN group (n=10), a sham injury+EN+Arg group (n=10), a burn+EN group (n=12), and a burn+EN+Arg group (n=12) and the mice in two experimental groups received a 20% total body surface area (TBSA), full-thickness scald burn on the back. Then, the burned mice were given a 175 kcal/kg body wt/day of conventional enteral nutrition or an isonitrogenous and isocaloric enteral nutrition supplemented with Arg by gastric gavage for 7 days. There was isonitrogenous and isocaloric intake in two experimental groups. The mice in two control groups received the same procedures as above, except for burn injury. On day 7 after injury, all mice among four groups were euthanized and the entire intestine was harvested. Intestinal immunoglobulin A (IgA) levels, total lymphocyte yield, and lymphocyte subpopulations in Peyer's patches were analyzed. Levels of IFN-gamma, IL-2, IL-4 and IL-10 in gut homogenates were also measured by ELISA. RESULTS: Total lymphocyte yield, numbers of lymphocyte subpopulations, and intestinal IgA levels in the EN+ARG group were higher than those in the EN group (p<0.05). Levels of gut tissue cytokines were significantly altered with enteral Arg supplementation: levels of IL-4 and IL-10 were increased, and levels of IFN-gamma and IL-2 declined, when compared with the EN-fed mice (p<0.05). CONCLUSIONS: The results of this study suggested that enteral nutrition supplemented with Arg has changed the cytokine concentrations in intestinal homogenates from a pro- to an anti-inflammatory profile, increased sIgA levels and changed lymphocytes in severely burned mice.

Echinacea purpurea and mucosal immunity.

This investigation examined the effects of Echinacea purpurea on mucosal immunity and the incidence and duration of upper respiratory tract infection (URTI). 32 subjects completed an exercise protocol known to affect mucosal immunity. Saliva was collected prior to and five minutes after completion of exercise testing. Subjects then took either a placebo (C) or Echinacea supplement (E) for 4 weeks and the testing procedure was repeated. Each time, s-IgA concentrations and saliva flow rate were measured and the secretion rate of s-IgA was calculated. In addition, standard logs indicating symptoms of URTI were completed throughout the study. Both groups demonstrated significant exercise induced reductions in s-IgA (C - 69 %; E - 43 %) and the secretion rate of s-IgA (C - 79 %; E - 53 %) at the beginning of the study (p < 0.05). Following the 4-week intervention, only the control group experienced the post intervention decrease in s-IgA (C - 45 %; E + 7 %) and the secretion rate of s-IgA (C - 45 %; E - 7 %). Further, while there was no significant difference in the number of URTI between groups, the reported duration was significantly different (C 8.6 days vs. E 3.4 days). The results suggest that Echinacea may attenuate the mucosal immune suppression known to occur with intense exercise and reduce the duration of URTI that subjects incur.

[Immunological and pathogenetic aspects of imunofan administration in aged patients with duodenal ulcer].

AIM: To specify immunological and pathogenetic aspects of imunophan use in aged patients with duodenal ulcer (DU). MATERIAL AND METHODS: Imunophan was given to 24 DU patients (mean age 62.0 +/- 1.5 years), in whom the size of ulcer varied from 0.6 to 2.1 cm. RESULTS: The patients on anti-ulcer therapy plus imunophan had a pain relief median 6.2 +/- 0.2 days (p < 0.001), control ones--11.8 +/- 0.1 days. The median of scarring duration in the test group was 16.2 +/- 0.2 days (p < 0.001), in the controls--23.8 +/- 0.3 days. In 3 (30.0%) cases the scars were rough. The count of T-lymphocytes in the study group increased from 53.1 +/- 0.6 to 65.1 +/- 0.2% (p < 0.001), of T-helpers/inductors--from 27.8 +/- 0.2 to 38.5 +/- 0.3% (p < 0.001), of cytotoxic T-lymphocytes--from 18.5 +/- 0.5 to 27.3 +/- 0.3 (p < 0.001), of B-lymphocytes--from 12.3 +/- 0.2 to 19.1 +/- 0.1% (p < 0.001). The therapy including imunophan reduced concentration of malonic dialdehide by 23.5%, trienic conjugates by 61.6%; raised the level of superoxide dismutase 1.6-fold, catalase 1.4-fold, glutathione reductase by 41.9% (p < 0.001). Neither immune status nor LPO-AOD changed significantly in patients on the basic therapy alone. CONCLUSION: The results obtained evidence for a positive action of imunophan on inflammation, immune status and antioxidant defense. Therefore, imunophan can be recommended as an adjuvant of basic anti-ulcer therapy in elderly and senile patients.

Effects of bovine colostrum supplementation on immune variables in highly trained cyclists.

The aim of this study was to investigate the influence of low-dose bovine colostrum protein concentrate (CPC) supplementation on selected immune variables in cyclists. Twenty-nine highly trained male road cyclists completed an initial 40-km time trial (TT(40)) and were then randomly assigned to either a supplement (n = 14, 10 g bovine CPC/day) or placebo group (n = 15, 10 g whey protein concentrate/day). After 5 wk of supplementation, the cyclists completed a second TT(40). They then completed 5 consecutive days of high-intensity training (HIT) that included a TT(40), followed by a final TT(40) in the following week. Venous blood and saliva samples were collected immediately before and after each TT(40), and upper respiratory illness symptoms were recorded over the experimental period. Compared with the placebo group, bovine CPC supplementation significantly increased preexercise serum soluble TNF receptor 1 during the HIT period (bovine CPC = 882 +/- 233 pg/ml, placebo = 468 +/- 139 pg/ml; P = 0.039). Supplementation also suppressed the postexercise decrease in cytotoxic/suppressor T cells during the HIT period (bovine CPC = -1.0 +/- 2.7%, placebo = -9.2 +/- 2.8%; P = 0.017) and during the following week (bovine CPC = 1.4 +/- 2.9%, placebo = -8.2 +/- 2.8%; P = 0.004). Bovine CPC supplementation prevented a postexercise decrease in serum IgG(2) concentration at the end of the HIT period (bovine CPC = 4.8 +/- 6.8%, P = 0.88; placebo = -9.7 +/- 6.9%, P = 0.013). There was a trend toward reduced incidence of upper respiratory illness symptoms in the bovine CPC group (P = 0.055). In summary, low-dose bovine CPC supplementation modulates immune parameters during normal training and after an acute period of intense exercise, which may have contributed to the trend toward reduced upper respiratory illness in the bovine CPC group.

Effect of Cha-em Thai mouthwash on salivary levels of mutans streptococci and total IgA.

The aim of this study was to investigate the effect of Cha-em Thai (Albizia myriophylla) mouthwash on the mutans streptococci (MS) and immunoglobulin A (IgA) level in saliva. Sixty-seven schoolchildren, age 6-12 years, with MS more than 1x10(5) cfu per milliliter of saliva were entered in this study. They were divided into two balanced groups according to their baseline MS counts (> or = 10(5) cfu/ml). Each group was randomly assigned to use either the Cha-em Thai mouthwash or the placebo mouthwash. After twice daily rinses with their mouthwash for 2 weeks, stimulated saliva were collected and analysed. The MS counts and IgA levels for the two groups were compared. Those rinsing with Cha-em Thai mouthwash showed a significant reduction in MS counts (p<0.05), but the IgA levels were not different. Those rinsing with the placebo mouthwash showed no statistically significant differences in the MS counts or the IgA levels (p>0.05). The results indicate that twice daily use of Cha-em Thai mouthwash can reduce the levels of MS in saliva.

Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans.

The effect of orally administrated gamma-aminobutyric acid (GABA) on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L-theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.

Effect of vitamin E supplementation on lymphocyte distribution in gut-associated lymphoid tissues obtained from weaned piglets.

Fifteen piglets were used to determine the effect of vitamin E supplementation on the number of CD4-immunoreactive (CD4+) T-lymphocytes, CD8-immunoreactive (CD8+) T-lymphocytes and IgA-immunoreactive (IgA+) B-lymphocytes per follicle in the Peyer's patch of distal ileum and the mesenteric lymph nodes of weaned piglets. Piglets, following a 3-day adaptation period after weaning, were assigned to one of three experimental groups: control (no vitamin E supplementation), vitamin E supplementation of 100 mg/kg of diet and vitamin E supplementation of 300 mg/kg of diet. Supplementation of vitamin E lasted for a period of 36 days. The basal diet contained 80 mg alpha-tocopherol/kg of diet. All piglets were killed at day 39 after weaning and samples of the distal ileum and adjacent mesenteric lymph nodes were collected. The number of cells for each lymphocyte subset was counted in the Peyer's patch and the mesenteric lymph nodes follicles, in cryostat sections processed for immunohistochemistry. Results showed that vitamin E supplementation (300 mg/kg diet) of piglets caused an increase (P < 0.05) in the number of IgA+ B-lymphocytes in the Peyer's patch, but not in the mesenteric lymph nodes, compared with the corresponding values in control animals. Vitamin E supplementation had no effect (P > 0.05) on the number of CD4+ and CD8+ T-lymphocytes in the follicles of the Peyer's patch and the adjacent mesenteric lymph nodes. Thus, vitamin E had relatively minor effects on distribution of the major immunocompetent cells in the gut. The numbers of CD4+ and CD8+ T-lymphocytes as well as IgA+ B-lymphocytes per follicle were higher by 26-77% (P < 0.05) in the mesenteric lymph nodes than the corresponding values in the Peyer's patch.

Effects of dietary quillaja saponin and curcumin on the performance and immune status of weaned piglets.

The objective of this study was to determine whether dietary quillaja saponin and curcumin (extract of turmeric) can modify piglet immune status and performance immediately after weaning. Piglets (n = 192) were weaned at 29 +/- 0.1 d and allocated to treatment (six replicates of eight pig per treatment) accounting for weight, litter, and gender, using a 2 x 2 factorial arrangement. Factors were diets with or without (as-fed basis) quillaja saponin (750 mg/kg during wk 1, 300 mg/kg during wk 2 to 3) and with or without dietary curcumin (200 mg/kg). Diets were fed ad libitum for 20 d after weaning. Feed intake was measured daily. Piglets were weighed at weaning, d 7, 14, and 20 after weaning. On each of d 6 and 20 after weaning, eight pigs per treatment were sacrificed for blood and tissue collection. Treatment had no effect on piglet growth. The ADFI and G:F were similar for all treatments between d 0 and 14 of the trial. Between d 15 and 20, ADFI and G:F were lower in quillaja-supplemented piglets (ADFI = 621 vs. 572 g/d; G:F = 0.75 vs. 0.85; P < 0.05). Serum immunoglobulin (Ig) G, IgA, interferon-gamma, and C-reactive protein (CRP) did not differ among treatments on d 6 after weaning. On d 20, IgG and CRP were greater (P < 0.05) in saponin-supplemented pigs (IgG = 17.5 vs. 11.4 mg/mL; CRP = 26.98 vs. 12.5 mg/mL). Small intestine villus and crypt measurements did not differ among treatments on either d 6 or 20. Saponin supplementation during the postweaning period seemed to potentiate an immune response in the weaned piglet but had a detrimental effect on the utilization of feed. Dietary curcumin had no influence on any measured aspect of pig performance or immune status.

Stimulatory effect of a dietary casein phosphopeptide preparation on the mucosal IgA response of mice to orally ingested lipopolysaccharide from Salmonella typhimurium.

The effect on immunoglobulin production of a commercially available casein phosphopeptide preparation (CPP-III) consisting mainly of bovine alpha s2-casein (1-32) and beta-casein (1-28) in mice that had orally ingested lipopolysaccharide (LPS) from Salmonella typhimurium was investigated. No significant difference in body weight gain was observed between the mice fed on the CPP-III-added diet and those fed on the control diet. The mice fed on the CPP-III-added diet exhibited similar serum and intestinal IgG, IgM, and IgE responses towards LPS to those fed on the control diet. In contrast, fecal and intestinal anti-LPS IgA and total IgA in mice fed on the CPP-III-added diet were significantly higher than in those fed on the control diet. Spleen cells from mice fed on the CPP-III-added diet produced larger amounts of IgA, IL-5, and IL-6 than cells from mice fed on the control diet. These results suggest that dietary casein phosphopeptide may protect a host from invasion of the intestinal mucosa by food-born pathogenic microorganisms.

Dietary fructooligosaccharides induce immunoregulation of intestinal IgA secretion by murine Peyer's patch cells.

Probiotic supplements induce immunological responses in the host, and dietary fructooligosaccharides (FOS) stimulate the growth of selected intestinal microflora. In this study we investigated the immunological influences of orally administrated FOS. BALB/c mice were orally administered 0-7.5% FOS for 6 weeks, and the intestinal mucosal immune responses were measured. In the 2.5%-FOS group, fecal IgA was significantly increased. IgA secretion by Peyer's patch (PP) cells was upregulated in a dose-dependent way in response to FOS and CD4+ T cells from PP showed a dose-dependent increase in production of interferon-gamma and interleukin (IL) 10, and a high response in production of IL-5 and IL-6. In contrast, FOS suppressed serum IgG1. Our findings suggest that FOS supplementation changes the intestinal environment of microflora, and leads to upregulation of IgA secretion in CD4+ PP cells in intestinal mucosa, and to suppression of the systemic immune response to type 2 helper T (Th2) dominant.

Suppressive effects of Perilla frutescens on IgA nephropathy in HIGA mice.

BACKGROUND: Perilla frutescens (perilla) is a herbal medicine used in Japanese traditional Kampo medicine. The present study was conducted to evaluate the anti-nephritic effects of perilla in HIGA mice that spontaneously develop high levels of serum immunoglobulin A (IgA) along with mesangial IgA deposition. METHODS: A perilla decoction and its major active constituent, rosmarinic acid (RsA), were orally administrated to 10-week-old HIGA mice for 16 weeks. At study completion, we measured proteinuria and serum IgA levels and generated histological scores from kidney specimens. In addition, we measured concentrations of IgA in culture media of intestinal Peyer's patch cells and spleen cells obtained from the HIGA mice. RESULTS: Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in HIGA mice. Cultured Peyer's patch cells and spleen cells from perilla-treated mice produced significantly less IgA than controls. Rosmarinic acid, by itself, suppressed serum IgA levels and glomerular IgA deposition in HIGA mice. Cultured spleen cells from RsA-treated mice produced less IgA than controls. CONCLUSIONS: The perilla decoction may suppress IgA nephropathy, in part, through modulation of the intestinal mucosal immune system. These effects were caused by RsA acting synergistically with other constituents.

Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels.

BACKGROUND: Total parenteral nutrition (TPN) prevents progressive malnutrition but fails to maintain intestinal gut-associated lymphoid tissue (GALT) or established respiratory antiviral or antibacterial mucosal immunity. Our previous work demonstrated that decreases in intestinal immunoglobulin A (IgA) were associated with decreases in Th2-type IgA-stimulating cytokines, interleukin (IL)-4 and IL-10. Because glutamine supplementation of TPN partially preserves respiratory defenses and normalizes GALT, we investigated the ability of parenteral glutamine to normalize respiratory and intestinal IgA levels and measured Th2 cytokines in intestinal homogenates. METHODS: Animals were cannulated and randomly assigned to receive chow (n = 17), TPN (n = 18), or an isonitrogenous, isocaloric TPN solution formulated by removing the appropriate amount of amino acids and replacing them with 2% glutamine (n = 18) for 5 days. Respiratory tract and intestinal washings were obtained for IgA and the intestine homogenized and analyzed for IL-4 and IL-10. RESULTS: TPN decreased intestinal and respiratory IgA in association with decreases in intestinal IL-4 and IL-10 compared with chow-fed animals. Glutamine significantly improved respiratory and intestinal IgA levels, significantly improved IL-4 compared with TPN animals, and maintained IL-10 levels midway between chow-fed and TPN animals. CONCLUSIONS: Glutamine-enriched TPN preserved both extraintestinal and intestinal IgA levels and had a normalizing effect on Th2-type IgA-stimulating cytokines.

Effect of dehydroepiandrosterone (DHEA) on intestinal mucosal immunity in young adult and aging rats.

The present study assesses the effectiveness of oral DHEA on the intestinal mucosal immune response in aging rats. Young adult (6 months) and aging (21 months) female rats received powdered rat chow with or without 0.2% DHEA for 23 days. The animals were immunized intraduodenally with either cholera toxin (CTx) or vehicle alone and boosted two weeks later. Seven days after boosting, serum, bile, small intestinal tissue, and liver were collected for analysis. Anti-CTx IgA antibody titers were measured in serum and bile and the concentration of anti-CTx antibody containing cells (ACCs) in the small intestinal lamina propria and liver were determined by quantitative immunohistochemistry. Intergroup comparisons indicated that there was only one significant difference in serum and none in bile anti-CTx IgA titers between CTx-immunized animals fed DHEA or the diet alone. Immunohistochemical analysis determined that the density and distribution patterns of ACCs within the lamina propria were unaffected by DHEA. Both DHEA-treated and control young immunized animals exhibited similar numbers of ACCs. Only 40% of the aging rats responded to intraduodenal immunization with CTx, as determined by the presence of ACCs in the intestine, regardless of the presence or absence of DHEA in the diet. These data suggest that DHEA in the diet does not enhance the intestinal mucosal immune response to intraduodenal CTx in either young adult or aging rats.

Endogenous cytokine expression profiles in retinoic acid-induced IgA production by LPS-stimulated murine splenocytes.

All-trans-retinoic acid (RA) enhances IgA production by LPS-stimulated murine splenocytes. After stimulation by RA and LPS, or by LPS alone, total RNA was extracted from cultured cells on Days 1 to 4, and the kinetics of expression of various cytokine mRNAs were analyzed by the RT-PCR method. RA induced the expression of IL-5 and TGF-beta 2 mRNAs in the LPS-stimulated cells. In addition, the expression of IL-6 and IL-2 mRNAs was more intensive in RA-stimulated cells than in unstimulated cells. TGF-beta 1 and TGF-beta 3 mRNAs were constitutively expressed in both culture groups. RA enhanced IgA production by LPS-stimulated spleen cells but not that by LPS-stimulated mu(+) naive splenic B-cells. For RA-induced IgA production, the B-cells required T-cells or the culture supernatant from RA-stimulated T-cells. Furthermore, exogenous IL-5 replaced the T-cell requirement, at least in part, in RA-induced IgA production by LPS-stimulated B-cells. This reaction was partially inhibited by anti-TGF-beta-neutralizing antibodies. These findings suggest that RA induces IgA production by (IL-5 + LPS)-stimulated B-cells in TGF-beta-independent and TGF-beta-dependent manners.

Immunoglobulin concentrations in serum and tissues of vitamin A-deficient broiler chicks after Newcastle disease virus vaccination.

The effect of all-trans retinol and retinoic acid (RA) on the local and systemic immune system of broiler chicks was examined. Chicks fed diets supplemented with .2 micrograms retinol/g of diet had significantly greater serum immunoglobulin IgG, IgM, and IgA concentrations 5 wk after primary vaccination with live B1 strain of Newcastle disease virus (NDV) than did chicks fed 2 micrograms retinol/g of diet. Eight days after a second vaccination with an inactivated La Sota strain of NDV, serum, intestinal, and tracheal IgG and IgM concentrations were higher in chicks fed a diet without retinol or retinoic acid (RA) than in chicks fed either 2 micrograms of retinol or RA/g of diet, respectively. Despite an increase in serum immunoglobulin concentration, serum antibody titer in response to the second NDV vaccination was significantly lower in chicks fed a vitamin A-deficient diet than in chicks fed adequate retinol and RA-supplemented diets. Eight days after revaccination, IgA concentrations in bile were also significantly lower in vitamin A-deficient chicks than in controls. Serum IgG, IgM, IgA, biliary IgA, and antibody responses were greater in chicks fed diets supplemented with 2 micrograms of RA/g of diet than in chicks fed an equivalent amount of vitamin A in the form of retinol.