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| Title: |
Modulation of the Immune System by Human Rhinoviruses. |
| Author(s): |
Kirchberger S, Majdic O, Stockl J. |
| Human rhinoviruses (HRV) are the major cause of the common cold, one of the most frequent infectious diseases in humans. Though HRV infections of the upper respiratory tract are usually rather harmless, there is increasing evidence that HRV sets the stage for more dangerous pathogens, elicits asthmatic exacerbations, severe diseases in the lower respiratory tract and even autoimmunity. The pathogenic mechanisms of HRV infections leading to such complications are still poorly understood. It is a common strategy of pathogens to manipulate our immune system in order to evade an efficient immune response. A major characteristic of HRV is a high degree of species specificity. Thus, analyzing the potential immune evasion mechanisms used by HRV will be helpful for a better understanding of the pathogenesis of the common cold and may contribute to a better understanding of the human immune system as well. In this review we want to illuminate what is known about potential immune escape mechanisms used by HRV and discuss how such disturbances might lead to a suppressed and dysregulated immune competence in man. Copyright (c) 2007 S. Karger AG, Basel. |
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Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice. |
| Author(s): |
Rowe AM, Brundage KM, Schafer R, Barnett JB |
| Atrazine is a widely used herbicide applied to corn, sugar and other crops as a broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that prenatal/lactational exposure to atrazine alters adult immune function. Pregnant Balb/c dams were exposed subcutaneously for 21 days via time release pellets to 700 microg per day of atrazine beginning between days 10 and 12 of pregnancy. Prenatal/Lactational exposure caused no overt physical malformations in the offspring and had no effect on the number of litters carried to term or the litter size. Upon reaching early adulthood (approximately 3 months of age), the state of their immune system was evaluated. There were no changes in body weight or in the organ to body weight ratio of the spleen. Additionally, no changes were observed in the number of CD8+ T cell, CD4+ T cell, or B220+ B cell subpopulations in the spleen. T cell function was assessed by measuring proliferation and cytolytic activity after in vitro allogeneic stimulation. Male mice which had been prenatally/lactationally exposed to atrazine had an increase in both T cell proliferation and cytolytic activity. The humoral immune response was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP). There was a significant increase in the number of HKSP-specific IgM secreting B cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as atrazine is a widespread environmental contaminant, this immunopotentiation raises concerns that it may potentiate clinical diseases, such as autoimmune disease and hypersensitivity, and needs to be carefully monitored and studied. |
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Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. |
| Author(s): |
Bobat R., Coovadia, H., Stephen C., Naidoo K. L., McKerrow N., Black, R. E., Moss, W. J |
| BACKGROUND: Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence. METHODS: We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol. FINDINGS: The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001). INTERPRETATION: Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea. RELEVANCE TO PRACTICE: Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection. |
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Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects. |
| Author(s): |
Huber R., Rostock M., Goedl R., Ludtke R., Urech K., Buck S., Klein R. |
| OBJECTIVE: Various immunological effects have been reported during application of mistletoe preparations. Because these data are heterogeneous, we performed a placebo controlled study to investigate (1) effects on peripheral granulocyte and eosinophil counts, (2) related cytokine levels and (3) whether effects are related to mistletoe lectin (ML). METHODS: 43 volunteers were randomized to receive the mistletoe plant extract Iscador Quercus spezial (IQ), purified ML, IQ which was depleted from ML, or placebo subcutaneously twice per week for 8 weeks. Weekly, differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells (PBMC) were analyzed. RESULTS: Leukocyte-, granulocyte-, and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group. Furthermore, a significant increase of antigen-induced production of GM-CSF, IL-5 and IFNgamma by PBMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo. Severe side effects did not occur in any of the subjects. CONCLUSIONS: Treatment with IQ or ML stimulates the production of GM-CSF, IL-5 and IFNgamma by PBMC, and this is accompanied by an increase of eosinophil- and granulocyte-counts. These observations may, therefore, open rational therapeutic indications for mistletoe extracts. |
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Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice. |
| Author(s): |
Kodama N, Murata Y, Nanba H. |
| We have reported that D-Fraction, a polysaccharide extracted from the edible maitake mushroom (Grifola frondosa), activates immunocompetent cells, thereby eliciting antitumor activity. To extend the application of D-Fraction as a nutritional supplement for healthy people as well as treatment for those with cancer, we investigated the effects of D-Fraction on the immune system in normal C3H/HeJ mice. Splenocytes from mice administered D-Fraction intraperitoneally for 17 consecutive days were cultured, and the culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-12 production by antigen-presenting cells (APCs), including macrophages and dendritic cells, and also for the T helper (Th)-1 cytokine interferon (IFN)-gamma and the Th-2 cytokines IL-4 and IL-10. The level of IL-10 as well as those of NO and IFN-gamma were increased by D-Fraction as compared with the control, in which the serum immunoglobulin E level was increased. The results suggest that D-Fraction induced a Th-2 dominant response through the activation of macrophages, resulting in the enhancement of humoral immunity rather than cell-mediated immunity. Furthermore, an increase in the percentage ratio of CD69 and CD89 expression on major histocompatibility complex II(+) cells revealed activation of APCs 4 h after D-Fraction administration. These results indicate that D-Fraction enhances both the innate and adaptive arms of the immune response in normal mice. Therefore, its administration may enhance host defense against foreign pathogens and protect healthy individuals from infectious diseases. |
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Title:
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Serum zinc and pneumonia in nursing home elderly. |
| Author(s): |
Meydani SN, Barnett JB, Dallal GE, Fine BC, Jacques PF, Leka LS, Hamer DH. Nutritional Immunology Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA. |
| BACKGROUND: Zinc plays an important role in immune function. The association between serum zinc and pneumonia in the elderly has not been studied. OBJECTIVE: The objective was to determine whether serum zinc concentrations in nursing home elderly are associated with the incidence and duration of pneumonia, total and duration of antibiotic use, and pneumonia-associated and all-cause mortality. DESIGN: This observational study was conducted in residents from 33 nursing homes in Boston, MA, who participated in a 1-y randomized, double-blind, and placebo-controlled vitamin E supplementation trial; all were given daily doses of 50% of the recommended dietary allowance of essential vitamins and minerals, including zinc. Participants with baseline (n = 578) or final (n = 420) serum zinc concentrations were categorized as having low (<70 mug/dL) or normal (>/=70 mug/dL) serum zinc concentrations. Outcome measures included the incidence and number of days with pneumonia, number of new antibiotic prescriptions, days of antibiotic use, death due to pneumonia, and all-cause mortality. RESULTS: Compared with subjects with low zinc concentrations, subjects with normal final serum zinc concentrations had a lower incidence of pneumonia, fewer (by almost 50%) new antibiotic prescriptions, a shorter duration of pneumonia, and fewer days of antibiotic use (3.9 d compared with 2.6 d) (P |
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Title:
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Ingestion of a dietary supplement containing dehydroepiandrosterone (DHEA) and androstenedione has minimal effect on immune function in middle-aged men. |
| Author(s): |
Kohut ML, Thompson JR, Campbell J, Brown GA, Vukovich MD, Jackson DA, King DS. |
| OBJECTIVE: This study investigated the effects of four weeks of intake of a supplement containing dehydroepiandrosterone (DHEA), androstenedione and herbal extracts on immune function in middle-aged men. DESIGN: Subjects consumed either an oral placebo or an oral supplement for four weeks. The supplement contained a total daily dose of 150 mg DHEA, 300 mg androstenedione, 750 mg Tribulus terrestris, 625 mg chrysin, 300 mg indole-3-carbinol and 540 mg saw palmetto. MEASUREMENTS: Peripheral blood mononuclear cells were used to assess phytohemagglutinin(PHA)-induced lymphocyte proliferation and cytokine production. The cytokines measured were interleukin (IL)-2, IL-4, IL-10, IL-1beta, and interferon (IFN)-gamma. Serum free testosterone, androstenedione, estradiol, dihydrotestosterone (DHT) were also measured. RESULTS: The supplement significantly increased serum levels of androstenedione, free testosterone, estradiol and DHT during week 1 to week 4. Supplement intake did not affect LPS or ConA proliferation and had minimal effect on PHA-induced proliferation. LPS-induced production of IL-1beta, and PHA-induced IL-2, IL-4, IL-10, or IFN-gamma production was not altered by the supplement. The addition of the same supplement, DHEA or androstenedione alone to lymphocyte cultures in vitro did not alter lymphocyte proliferation, IL-2, IL-10, or IFN-gamma, but did increase IL-4. In addition, serum HDL-C concentration significantly declined. CONCLUSION: These findings suggest that, although chronic intake of a complex dietary supplement containing DHEA, androstenedione and herbal extracts increases serum androgen levels, it has minimal effect on immune function in middle-aged men. |
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Title:
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Padma 28, a traditional Tibetan herbal preparation inhibits the respiratory burst in human neutrophils, the killing of epithelial cells by mixtures of oxidants and pro-inflammatory agonists and peroxidation of lipids. |
| Author(s): |
Gingsburg I, Sadovnik M, Sallon S, Milo-Goldzweig I, Mechoulam R, Breuer A, Gibbs D, Varani J, Roberts S, Cleator E, Singh N |
| Both aqueous and methanolic fractions derived from the Tibetan preparation Padma 28 (a mixture of 22 plants) used as an anti-atherosclerotic agent, and which is non-cytolytic to a variety of mammalian cells, were found to strongly inhibit (1) the killing of epithelial cells in culture induced by “cocktails” comprising oxidants, membrane perforating agents and proteinases; (2) the generation of luminol-dependent chemiluminescence in human neutrophils stimulated by opsonized bacteria; (3) the peroxidation of intralipid (a preparation rich in phospholipids) induced in the presence of copper; and (4) the activity of neutrophil elastase. It is proposed that Padma 28 might prove beneficial for the prevention of cell damage induced by synergism among pro-inflammatory agonists which is central in the initiation of tissue destruction in inflammatory and infectious conditions. |
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Title:
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The Effect of Padma 28, a Traditional Tibetan Herbal Preparation, on Human Neutrophil Function. |
| Author(s): |
Matzner Y, Sallon S |
| Human neutrophils were studied in vitro in the presence of the herbal preparation Padma 28. At concentrations higher than 0.3 mg/ml, the Padma 28 induced 02 production in unstimulated neutrophils. At lower concentrations, 02 production was inhibited in phorbol myristate acetate (PMA) stimulated cells. Lysozyme release by PMA and opsonized zymosan-stimulated cells was inhibited by Padma 28 at a concentration dependent manner. On the other hand, random and directed migration and adhesion to nylon fibers were not affected. These results suggest that Padma 28 may have anti-inflammatory activity whose mechanism remains to be elucidated. |
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Title:
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Influence of PADMA 28 on the spontaneous bactericidal activity of blood serum in children suffering from recurrent infections of the respiratory tract |
| Author(s): |
Jankowski S, Jankowski A, Zielinska S, Walczuk M, Brzosko WJ |
| The effect of PADMA 28 on spontaneous bactericidal activity (SBA) of blood serum was tested in 19 children suffering from recurrent infections of the respiratory tract (RIRT). SBA was tested against three bacterial strains; Salmonella typhimurium 568, and Escherichia coli strains 044 and 055. A considerable increase (bactericidal index <2) of SBA was noted in 12 children (63.1%). In four children (21%) the increase of SBA was less pronounced (bactericidal index >2). In three children (15.7%) no effect of PADMA 28 on SBA of the serum was observed. |
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Title:
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Influencing recurring respiratory system infections in children via immunostimulation |
| Author(s): |
Mansfeld HJ |
| Nonspecific respiratory illnesses play a dominant part in childhood. Causal therapy to improve the immunologic defence mechanism does not exist as yet. Treatment with so-called immunostimulating and immunoregulating products is widespread, their effectiveness, however, is controversial. PADMA 28, a Tibetan herbal remedy, appears to have demonstrable immunoregulating characteristics. It also has a positive influence on the frequency and severity of respiratory infections in children. |
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Title:
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Immunostimulation in recurrent respiratory tract infections therapy in children |
| Author(s): |
Prusek W, Jankowski A, Radomska G, Wieczorek E, Podwysocka M |
| Selected immunologic parameters and effectivity of immunotherapy was evaluated in 117 children (12-month – 10-year-old) suffering from recurrent respiratory tract infections. All the children displayed a profound depression of T lymphocytes number, which resemble the situation seen in AIDS patients. An increase of serum IgM concentration was also noted. Immunotherapy included treatment with the following preparations: TFX and Levamisol which stimulate T cells functions, Broncho-Vaxom which stimulates specific antibody production and a complex herb preparation PADMA showing undefined general stimulatory activity. Separate group of children was subjected to climatotherapy in Czerniawa Sanatorium and received no immunostimulants. All methods of treatment employed had beneficial effect. The highest percentage of positive results was obtained in children receiving TFX and Levamisol. In all groups under study, an elevation of T cells percentage was observed. This was especially evident in Levamisol treated patients. There was no correlation, however, between T cells number and clinical improvement. |
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Title:
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Treatment with PADMA 28 of children with recurrent infections of the respiratory tract |
| Author(s): |
Jankowski A, Drabik E, Szysko Z, Stasiewin W, Brzosko WJ |
| 61 children with recurrent infections of the respiratory tract were treated with a herbal, the immune system stimulating drug. During the treatment and the 9 month follow-up the frequency of infections diminished in 80.4% of the cases. An aggravation of the clinical state and side effects were not observed. The age-related IgG, IgM and IgA levels did not change while the percentage of early and late T-lymphocytes, T-gamma lymphocytes and the phagocytic activity of granulocytes increased significantly. The action is explained by immunocorrective properties of the drug. |
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