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S N Meydani

Publications and source records attributed to S N Meydani.

At least 19 recordsLinked to original sources
PubMed1997

Enhanced expression of inducible cyclooxygenase with age in murine macrophages.

Macrophages (Mphi) from old mice produce more PGE2 than those from young mice, contributing to the dysregulation of the immune and inflammatory responses with age. This study was conducted to determine the mechanisms of the age-associated increase in Mphi PGE2 production. PGE2 production is influenced by the availability of the substrate arachidonic acid and by activity of the enzyme cyclooxygenase (Cox). We demonstrate that when the substrate is not the limiting factor, Mphi from old mice have significantly higher LPS-stimulated Cox activity than young mice, indicating that the age-associated increase in PGE2 production is due to increased enzyme activity and not to changes in substrate level. Cox activity is determined by the enzyme level and requires hydroperoxide for activation. Of the two Cox isoforms, Cox 1 is constitutively expressed in nearly all cells; whereas Cox 2 is induced by a wide range of ligands. Analysis of accumulated and de novo synthesis of constitutive Cox 1 and inducible Cox 2 proteins showed no age-related difference in Cox 1 protein levels, but Mphi from old mice had higher accumulated and newly synthesized LPS-stimulated Cox 2 protein levels than young mice. Furthermore, Mphi from old mice had higher LPS-stimulated levels of Cox 2 mRNA compared with those from young mice. Clearly, the age-associated increase in LPS-stimulated PGE2 production is due to increased Cox activity resulting from higher Cox 2 protein and mRNA expression. These findings have significant implications for age-associated immune and inflammatory dysregulation as well as the development of preventive and therapeutic strategies against them.

Aging↗
PubMed1997

Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial.

OBJECTIVE: To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects. DESIGN: Randomized, double-blind, placebo-controlled intervention study. SETTING AND PARTICIPANTS: A total of 88 free-living, healthy subjects at least 65 years of age. INTERVENTION: Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. RESULTS: Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum alpha-tocopherol (vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed. CONCLUSIONS: Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.

Aged↗
PubMed1997

Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E.

The aging process is associated with a decline in T cell-mediated immunity, including decreased interleukin (IL)-2 production and mitogen-induced T cell proliferation. Because macrophages (M phi) from old mice have higher production of prostaglandin (PG) E2 than young mice, and PGE2 has been shown to suppress T cell-mediated function, we hypothesized that increased production of PGE2 would contribute to decreased T cell function with aging and that decrease in PGE2 production by dietary antioxidants would enhance T cell-mediated function. Experiments were conducted in which combinations of purified M phi and T cells (> 95% pure) from young or old C57BL/6N1A mice were cultured together. Co-cultures containing T cells and M phi from old mice had reduced ConA-stimulated proliferation and IL-2 secretion than those consisting of T cells and M phi from young mice. Addition of M phi from old mice suppressed proliferation and IL-2 secretion by T cells from young mice. Likewise, T cells from old mice secreted more IL-2 when cultured with M phi from young mice compared to those cultured with M phi from old mice. Addition of PGE2, at concentrations produced by old M phi, decreased proliferation and IL-2 production by young but not old T cells. Neither addition of H2O2 at physiological levels, nor catalase changed the response of cultures from young or old mice. However, addition of indomethacin and the antioxidant nutrient vitamin E, both of which decreased PGE2 production, improved T cell proliferation and IL-2 production. These experiments demonstrate that increased production of PGE2 by M phi contributes to the age-associated decline in T cell function. Vitamin E improves T cell responsiveness in old mice mostly by reducing M phi PGE2 production, although a direct effect of vitamin E on T cells was also observed.

Aging↗
PubMed1997

Vitamin E status and immune function.

Evidence from animal and human studies indicates that vitamin E plays an important role in the maintenance of the immune system. Even a marginal vitamin E deficiency impairs the immune response, while supplementation with higher than recommended dietary levels of vitamin E enhances humoral and cell-mediated immunity. The current RDA level of vitamin E prevents clinical deficiency syndrome but in some situations, especially in older subjects or in a disease state, fails to maintain optimal host defense. The immunological parameters reviewed are all sensitive to changes in the availability of vitamin E and, therefore, may reflect the vitamin E status of a given individual more accurately than conventional methods.

Animals↗
PubMed1997

Vitamin E supplementation decreases lung virus titers in mice infected with influenza.

Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in young mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25-fold vs. 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic T lymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.

Animals↗
PubMed1997

Short- and long-term beta-carotene supplementation do not influence T cell-mediated immunity in healthy elderly persons.

Supplementation of healthy elderly persons with beta-carotene has been considered a way to enhance immune responses. In study 1 the short-term effect of beta-carotene (90 mg/d for 3 wk) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of healthy elderly women. In study 2 the long-term effect of beta-carotene (50 mg every other day for 10-12 y) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of men enrolled in the Physicians' Health Study. Subjects from both studies taking active supplements had significantly greater plasma beta-carotene concentrations than did subjects taking placebo. The pre- to postintervention change in delayed-type hypersensitivity skin test responses between beta-carotene and placebo groups in the short-term study was not significantly different, nor was the response between treatment groups in the long-term study. There were no significant effects due to beta-carotene supplementation on in vitro lymphocyte proliferation, production of interleukin 2, or production of prostaglandin E2 as a result of short- or long-term beta-carotene supplementation. In addition, there were no differences in the profiles of lymphocyte subsets [total T cells (CD3+), T helper cells (CD4+), T cytotoxic-suppressor cells (CD8+), and B cells (CD19+)] due to short- or long-term beta-carotene supplementation, nor were there differences in percentages of CD16+ natural killer cells or activated lymphocytes (cells expressing interleukin 2 transferrin receptor) due to long-term beta-carotene supplementation. Consistent results from these two trials show that beta-carotene supplementation did not have an enhancing or suppressive effect on T cell-mediated immunity of healthy elderly.

Aged↗
PubMed1997

Effect of vitamin E supplementation on prostaglandin concentrations in aspirin-induced acute gastric injury in aged rats.

Nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin, frequently cause gastric mucosal injury in the elderly. Impairment of prostaglandin synthesis is a crucial step by which aspirin attenuates mucosal defense capacity. Vitamin E has been shown to decrease prostanoid concentrations, which implies an ulceropermissive effect of vitamin E. To assess the effect of vitamin E on aspirin-induced gastric injury and mucosal prostanoid concentrations, 20 male rats aged 20 mo were divided into two groups and fed diets containing either 30 (physiologic requirement) or 500 mg all-rac-alpha-tocopheryl acetate/kg. After 6 wk, all rats received two intragastric doses of aspirin (1.4 mumol/kg body wt). A third group of six animals fed the high-vitamin E diet received a vehicle solution without aspirin. Mucosal samples for vitamin E and prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane A2 measurements were collected. The prevalence and degree of mucosal lesions were not significantly different among all groups. Rats fed the high-vitamin E diet had significantly higher mucosal vitamin E concentrations than rats fed the low-vitamin E diet. Mucosal concentrations of all three prostanoids were 95% lower in aspirin-treated rats than in controls (P = 0.0001 in all instances). The high-vitamin E diet group had significantly lower mucosal 6-keto-prostaglandin F1 alpha concentrations (P = 0.02) than the low-vitamin E diet group, indicating decreased prostacyclin formation, whereas concentrations of prostaglandin E2 and thromboxane A2 were similar in the aspirin-treated groups. Aspirin markedly reduced mucosal prostanoid concentrations in rats, without apparent effects on gastric injury, whereas vitamin E supplementation significantly reduced mucosal 6-keto-prostaglandin F(1 alpha) concentrations. Nevertheless, vitamin E supplementation did not result in more gastric injury in aspirin-treated rats than in controls.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

The effect of progressive resistance training in rheumatoid arthritis. Increased strength without changes in energy balance or body composition.

OBJECTIVE: To demonstrate the feasibility of high-intensity progressive resistance training in rheumatoid arthritis (RA) patients compared with healthy control subjects. METHODS: Eight subjects with RA, 8 healthy young subjects, and 8 healthy elderly subjects underwent 12 weeks of high-intensity progressive resistance training, while 6 elderly subjects performed warm-up exercises only. Fitness, body composition, energy expenditure, function, disease activity, pain, and fatigue were measured at baseline and followup. RESULTS: All 3 training groups demonstrated similar improvements in strength compared with the change among control subjects (RA group 57% [P < 0.0005], young exercise group 44% [P < 0.01], elderly exercise group 36% [P < 0.05]). Subjects with RA had no change in the number of painful or swollen joints but had significant reductions in self-reported pain score (21% [P < 0.05]) and fatigue score (38% [P = 0.06]), improved 50-foot walking times (mean +/- SD 10.4 +/- 2.2 seconds versus 8.3 +/- 1.5 seconds [P < 0.005]), and improved balance and gait scores (48.9 +/- 3.8 versus 50.4+/- 2.0 [P = 0.07]). CONCLUSION: High-intensity strength training is feasible and safe in selected patients with well-controlled RA and leads to significant improvements in strength, pain, and fatigue without exacerbating disease activity or joint pain.

Adult↗
PubMed1996

Effect of vitamin E on human aortic endothelial cell responses to oxidative injury.

Reactive oxygen species produced by the cells present in the arterial wall may cause oxidative damage to cellular components altering endothelial cell (EC) function. Changes in the EC function appear to play a key role in the pathogenesis of atherosclerosis. Human aortic endothelial cells (HAEC) were employed to investigate the protective role of vitamin E upon exposure of endothelial cells to oxidative stress in vitro. HAEC assimilate d-alpha-tocopherol from the media in a dose-dependent manner. Exposure of HAEC to 16.5 mM of the free radical generator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 16 h decreased cell viability (assessed by trypan blue exclusion) from 90 to 28%. HAEC preincubated with vitamin E at 15, 30, and 60 microM prior to the AAPH exposure resulted in a dose-dependent increase in resistance to oxidative stress and increased cell viability by 37, 66, and 85%, respectively. An increase in prostacyclin (PGI2) production by HAEC in response to AAPH exposure was correlated positively with cell damage and negatively with vitamin E concentration. Interleukin (IL)-1 production also increased in parallel with cell damage induced by AAPH. Vitamin E treatment significantly reduced IL-1 production after AAPH exposure. This modulatory role of vitamin E on HAEC function following exposure to an oxidative stress may reflect its antioxidant protection against lipid peroxidation.

Amidines↗
PubMed1996

Oral aspirin and ibuprofen increase cytokine-induced synthesis of IL-1 beta and of tumour necrosis factor-alpha ex vivo.

We investigated the effect of oral aspirin and ibuprofen on the ex vivo synthesis of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by stimulated peripheral blood mononuclear cells (PBMC) from healthy volunteers. Seven volunteers took 325 mg of aspirin daily for 14 days. Three weeks after ending aspirin medication, ex vivo IL-1 beta and TNF synthesis induced by exogenous IL-1 alpha was elevated threefold compared to the pre-aspirin value (P = 0.01 and P = 0.005, respectively). Using lipopolysaccharide (LPS) as a stimulus, no influence of oral aspirin was observed. The increase in cytokine synthesis did not parallel decreased synthesis of prostaglandin E2 (PGE2). Seven weeks after discontinuation of aspirin, cytokine and PGE-2 production returned to pre-aspirin levels. Another seven volunteers took 200 mg of ibuprofen daily for 12 days. Again, there was no effect on LPS- or Staphylococcus epidermidis-induced cytokine synthesis. However, IL-1 alpha-induced synthesis of IL-1 beta was elevated to a mean individual increase of 538% (P < 0.001) and synthesis of TNF was elevated to 270% (P < 0.001) at the end of ibuprofen medication and 2 weeks after discontinuation of ibuprofen. There were parallel increases in PGE2 and both returned to their pre-ibuprofen levels 5 weeks after stopping. Although inhibitors of cyclo-oxygenase blunt PGE2-mediated symptoms such as fever and pain, we conclude that short term use of either aspirin or ibuprofen results in a 'rebound' increase in cytokine-induced cytokine synthesis that is not observed in LPS-induced cytokines.

Administration, Oral↗
PubMed1996

Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates.

The effect of marine- and plant-derived n-3 polyunsaturated fatty acids (PUFAs) on T cell-mediated immune response was studied in cynomolgus monkeys. Animals were first fed a 14-wk baseline diet; 10 animals were then fed diets containing 1.3% or 3.3% of energy as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) which the other 10 were fed diets containing 3.5% or 5.3% of energy as alpha-linolenic acid (ALA) for two consecutive 14-wk periods. Both diets significantly decreased the percentage of T cells (except 1.3% EPA + DHA), T helper cells (except 1.3% EPA + DHA and 3.5% ALA), and T suppressor cells. Proliferative response of lymphocytes to T cell mitogens significantly increased after the diet containing 3.3% EPA + DHA. Interleukin 2 production significantly increased after the diets containing 1.3% and 3.3% EPA + DHA. No significant changes in mitogenic response or interleukin 2 production were found after ALA diets. Feeding 1.3% or 3.3% EPA + DHA or 5.3% ALA significantly suppressed prostaglandin E2 production in response to T cell mitogens. Plasma tocopherol concentrations were decreased significantly only in monkeys fed ALA diets. We conclude that after adjustment for the tocopherol concentration, marine-derived n-3 PUFAs but not plant-derived n-3 PUFAs increased T cell-mediated mitogenic response and interleukin 2 production. This is most likely due to diet-induced quantitative differences in cellular fatty acid composition and, thus, in prostaglandin E2 production and tocopherol status.

Animals↗
PubMed1996

Carotenoid and tocopherol concentrations in plasma, peripheral blood mononuclear cells, and red blood cells after long-term beta-carotene supplementation in men.

To determine the effects of long-term beta-carotene supplementation on concentrations of carotenoids and tocopherols in plasma and in blood cells, fasting blood was collected from 73 randomly selected physicians from the Boston area who are participating in the Physicians Health Study (PHS). The PHS is a randomized, placebo-controlled, double-blind study. In 1982, 22,071 male physicians were assigned to one of four treatments (325 mg aspirin alone, 50 mg beta-carotene alone, both, or neither) every other day. Plasma, peripheral blood mononuclear cells (PBMCs), and red blood cells (RBCs) from physicians who have participated in the study for approximately 12 y were analyzed for carotenoids and tocopherols. Compared with the placebo group, the supplemented group had higher beta-carotene concentrations in plasma (1.73+/-0.16 compared with 0.54+/-0.06 micromol/L0, RBCs (91.5+/-9.7 compared with 31.2+/-4.2 pmol/g hemoglobin), and PBMCs (61.6+/-10.3 compared with 15.5+/-2.5 pmol/10(7) cells). There were no differences in other carotenoids or tocopherols in plasma, RBCs, and PBMCs between these two groups. The beta-carotene concentrations. Plasma cryptoxanthin correlated with both RBC and PBMC cryptoxanthin concentrations but plasma lycopene correlated only with PBMC lycopene concentrations. These data suggest that plasma may not be the best indicator of carotenoid status. Furthermore, long-term beta-carotene supplementation in men results in higher beta-carotene concentrations in plasma, RBCs and PBMCs without lowering concentrations of other carotenoids or tocopherols.

Aged↗
PubMed1996

Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation.

Natural killer (NK) cell activity has been postulated to be an immunologic link between beta-carotene and cancer prevention. In a cross-sectional, placebo-controlled, double-blind study we examined the effect of 10-12 y of beta-carotene supplementation (50 mg on alternate days) on NK cell activity in 59 (38 middle-aged men, 51-64 y; 21 elderly men, 65-86 y) Boston area participants in the Physicians' Health Study. No significant difference was seen in NK cell activity due to beta-carotene supplementation in the middle-aged group. The elderly men had significantly lower NK cell activity than the middle-aged men; however, there was no age-associated difference in NK cell activity in men supplemented with beta-carotene. beta-carotene-supplemented elderly men had significantly greater NK cell activity than elderly men receiving placebo. The reason for this is unknown; however, it was not due to an increase in the percentage of NK cells, nor to an increase in interleukin 2 (IL-2) receptor expression, nor to IL-2 production. beta-carotene may be acting directly on one or more of the lytic stages of NK cell cytotoxicity, or on NK cell activity-enhancing cytokines other than IL-2, such as IL-12. Our results show that long-term beta-carotene supplementation enhances NK cell activity in elderly men, which may be beneficial for viral and tumoral surveillance.

Aged↗
PubMed1996

Effects of progressive resistance training on immune response in aging and chronic inflammation.

The effects of 12 wk of progressive resistance strength training on in vivo and in vitro immune parameters were evaluated in a controlled study of eight subjects with rheumatoid arthritis (RA), eight healthy young (22-30 yr), and eight healthy elderly (65-80 yr) individuals. Six healthy elderly (65-80 yr) nontraining control subjects were also evaluated to account for seasonal and psychosocial effects. Training subjects exercised at 80% of their one-repetition maximum and performed eight repetitions per set, three sets per session on a twice weekly basis. Peripheral blood mononuclear cell (PBMC) subpopulations, cytokine and prostaglandin (PG) E2 production, proliferative response, and delayed type hypersensitivity (DTH) skin response were measured before and after 12 wk of training. Training did not induce changes in PBMC subsets, interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF), IL-6, IL-2, or PGE2 production, lymphocyte proliferation, or DTH response in any of the training groups, compared with control subjects. These data suggest that 12 wk of high-intensity progressive resistance strength training does not affect immune function in young or elderly healthy individuals or subjects with RA.

Aged↗
PubMed1996

Effect of (n-3) polyunsaturated fatty acids on cytokine production and their biologic function.

Cytokines are important biologic mediators with tightly regulated production. Overproduction contributes to pathogenesis of acute and chronic inflammatory, autoimmune, atherosclerotic, and neoplastic diseases. Animal and human studies have shown that production of cytokines can be reduced by long-chain (n-3) polyunsaturated fatty acids (PUFA). This, in turn, results in reduction of the severity of certain autoimmune, inflammatory, and atherosclerotic diseases and reduces cytokine-induced anorexia. Because these cytokines are also involved in control of the host defense, substantial reduction in their production could impair normal immune response. In addition, increased intake of (n-3) PUFAs without adequate antioxidant protection could result in increased free radical formation and lipid peroxidation, leading to a reduction in T cell-mediated function, natural killer cell activity, and macrophage cytotoxicity. These risks associated with the intake of (n-3) PUFAs may be minimized without compromising its beneficial effects by the intake of appropriate levels of antioxidants such as vitamin E.

Appetite↗
PubMed1995

Antioxidants and immune response in aged persons: overview of present evidence.

The oxidant-antioxidant balance is an important determinant of immune cell function, including maintaining the integrity and functionality of membrane lipids, cellular proteins, and nucleic acids and controlling signal transduction and gene expression in immune cells. Optimal amounts of antioxidants are needed for maintenance of the immune response across all age groups. This need might be more critical, however, in aged persons. Age-associated dysregulation of immune response, particularly of T cell-mediated function, is well documented. The well-known age-related increase in free radical formation and lipid peroxidation contributes, at least in part, to this phenomenon. We summarize animal and human studies undertaken by ourselves as well as other investigators on the effects of antioxidants, vitamin E, beta-carotene, and glutathione on the immune response of aged persons. The underlying mechanisms for the antioxidant nutrients' effects as well as their health implications for aged persons are discussed.

Adjuvants, Immunologic↗