Vitamin E ingestion improves several immune functions in elderly men and women.

The effects of diet supplementation with the antioxidant vitamin E (200 mg daily) on several blood neutrophil, lymphocyte and natural killer cell functions have been investigated in healthy elderly men and women before supplementation, after 3 months of supplementation and 6 months after the end of supplementation (post-supplementation). In parallel, samples of healthy adult men and women were used as age controls. In elderly men and women, an impairment of immune functions was observed in comparison with the respective adult controls and the intake of vitamin E resulted in a significant enhancement of immune parameters in both elderly men and women, bringing their values close to those in the adults. These effects were not found in post-supplementation samples in several but not in all functions. The present findings suggest that supplementation with vitamin E can produce an improvement of immune functions and therefore of health in aged people.

Effect of acupuncture treatment on the immune function impairment found in anxious women.

It is presently accepted that emotional disturbances lead to immune system impairment, and that therefore their treatment could restore the immune response. Thus, the aim of the present work was to study the effect of an acupuncture treatment, designed specifically to relieve the emotional symptoms stemming from anxiety, on several functions (adherence, chemotaxis, phagocytosis, basal and stimulated superoxide anion levels, lymphocyte proliferation in response to phytohemagglutinin A (PHA) and natural killer (NK) activity) of leukocytes (neutrophils and lymphocytes) from anxious women. The acupuncture protocol consisted of manual needle stimulation of 19 acupoints, with each session lasting 30 min. It was performed on 34 female 30-60 year old patients, suffering from anxiety, as determined by the Beck Anxiety Inventory (BAI). Before and 72 hours after receiving the first acupuncture session, peripheral blood samples were drawn. In 12 patients, samples were also collected immediately after the first single acupuncture session and one month after the end of the whole acupuncture treatment, which consisted of 10 sessions during a year, until the complete remission of anxiety. Twenty healthy non-anxious women in the same age range were used as controls. The results showed that the most favorable effects of acupuncture on the immune functions appear 72 hours after the single session and persist one month after the end of the complete treatment. Impaired immune functions in anxious women (chemotaxis, phagocytosis, lymphoproliferation and NK activity) were significantly improved by acupuncture, and augmented immune parameters (superoxide anion levels and lymphoproliferation of the patient subgroup whose values had been too high) were significantly diminished. Acupuncture brought the above mentioned parameters to values closer to those of healthy controls, exerting a modulatory effect on the immune system.

Impairment of several immune functions in anxious women.

OBJECTIVE: Controversial results concerning immune function changes taking place in anxious subjects have been obtained. The aim of the present work was to study immune function in a group of anxious women. METHODS: Thirty-three anxious and 33 nonanxious age-matched women were included. Anxiety levels were determined by the Beck Anxiety Inventory. Peripheral blood samples were collected, and several leukocyte functions, as well as cytokine release, were studied. Plasma cortisol levels and total antioxidant capacity were also evaluated. RESULTS: The results showed diminished chemotaxis, phagocytosis, lymphoproliferation in response to phytohemagglutinin mitogen, natural killer activity, and interleukin-2 release, and augmented superoxide anion levels and tumor necrosis factor-alpha release in anxious women. Plasma cortisol was increased, while total antioxidant capacity was lowered in those subjects. CONCLUSIONS: The findings suggest impaired immune function and cytokine release in anxious women. This might be related to increased cortisol secretion, which would lead to oxidative stress reflected in lowered plasma total antioxidant capacity.

Changes with ageing in several leukocyte functions of male and female rats.

The impairment of the immune system with aging, or 'immunosenescence', appears to contribute to the increased morbidity and mortality of aged subjects. T cell functions and Natural Killer activity seem to be the immune responses most affected by ageing. Since the immune system works more efficiently in females than in males, we have studied the changes of several immune functions with age in rats of both sexes. In addition, we have investigated if ovariectomy, a model of menopause in rats, produces a loss of this gender-related advantage. In the present work, the changes with age (2, 6, 12, 14, 18, 22 and 24 months old) in lymphocyte chemotaxis, T lymphoproliferative response to the mitogen ConA, IL-2 release and Natural Killer activity of cells from axillary nodes and spleen of male and female rats as well as of females ovariectomized at 12 months of age have been studied. An age-related decrease was found in all investigated functions, with a slightly different evolution depending on the immune organ and gender considered. In general, the data obtained show that a certain degree of immunosenescence takes place with age in rats, with males being less immunocompetent than intact age-matched females, but showing an immune response similar to that of ovariectomized animals.

Characterization of monoaminergic systems in brain regions of prematurely ageing mice.

We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration ("slow mice") being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

An impairment of phagocytic function is linked to a shorter life span in two strains of prematurely aging mice.

In previous cross-sectional studies on Swiss mouse populations we have shown that at the same chronological age, animals that take longer to explore a simple T-maze (slow mice) are hyper-emotional and show an impairment of the immune system than those which quickly explore the maze (fast mice). Therefore, we have proposed that the slow mice are a model of prematurely aging mice (PAM). In the present work we have carried out a longitudinal study of age-dependent changes in key functions of phagocytic cells (peritoneal macrophages) such as phagocytosis and superoxide anion production in both male and female Swiss (outbred strain) and BALB/c (inbred strain) PAM and non-prematurely aging mice (NPAM). Gender differences were found showing the females better phagocytic and digestion capacities with concomitant longer life span. The PAM showed an impaired phagocytosis capacity and intracellular superoxide anion production as well as an increase of its extracellular production as compared to NPAM, which could be related to the shortened life span of those animals in both sexes and strains.

Effects of N-acetylcysteine on macrophage and lymphocyte functions in a mouse model of premature ageing.

In previous studies, we have observed that mice of the same strain and age show striking interindividual differences in behavior when exposed to a T-maze test. The animals that take longer to explore a T-shaped maze ("slow" animals) show high levels of emotionality/anxiety in other standard behavioral tests, prematurely aged immune functions, and a shorter life span, in comparison to "fast" mice. In these slow mice, which are a model of premature immunosenescence, the immune functions were improved after the ingestion of the thiolic antioxidant thioproline in the diet. In the present work, we studied the effects in vivo (0.1% w/w, for 4 weeks) and in vitro (0.001, 0.01, 0.1, 1, and 2.5 mM) of the thiolic antioxidant N-acetylcysteine (NAC) on different functions of peritoneal macrophages and lymphocytes from slow and fast adult Swiss mice. The results showed an improvement of all the functions studied, namely adherence to substrate, directed migration or chemotaxis, phagocytosis, and reactive oxygen species (ROS) production, after in vivo and in vitro treatment with NAC. The effect of this antioxidant was stronger in the cells from the slow than in those from the fast mice.

Relation of behaviour and macrophage function to life span in a murine model of premature immunosenescence.

According to our previous work, mice of the same strain and age show striking inter-individual differences in behaviour when exposed to a T-maze test. Further, the animals exploring the maze slowly (slow mice) or staying at the starting point (freezing behaviour), which show high levels of emotionality/anxiety in other standard behavioural tests, have a less competent immune system (earlier immunosenescence) than those which explore it quickly (fast mice). The present longitudinal study on OF-1 Swiss female mice confirms and extends the above findings. Thus, the animals showing a lower performance in the T-test (slow mice) which is accompanied by a poor neuromuscular coordination in a tightrope test, have a shorter life span than the good performers (fast mice). Moreover, the slow mice have a less competent immune system as regards the following functions of peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of particles and superoxide anion production. This suggests that, at the same chronological age and as regards their immune competence, the slow mice are biologically older than the fast mice. This agrees with current ideas on the close functional relationship between the nervous and the immune system in the physiological adaptation to stress, and supports the concept that an optimum level of performance of these two systems is needed to attain a long life span.

Changes in the antioxidant content of mononuclear leukocytes from mice with endotoxin-induced oxidative stress.

Oxidative stress, associated with a high production of reactive oxygen species (ROS) by immune cells, is involved in the endotoxic shock caused by endotoxin. This oxidative stress is linked to the inability of the immune cells to maintain adequate levels of antioxidants with free radical-scavenging action. Glutathione (GSH) and ascorbic acid (AA) are intracellular and extracellular antioxidants (ROS scavengers) that improve the leukocyte functions. Therefore, in the present work we have determined the reduced GSH and AA content in axillary nodes, spleen, thymus and peritoneal mononuclear leukocytes from BALB/c mice subjected to lethal endotoxic shock produced by intraperitoneal injection of E. coli lipopolysaccharide (LPS, 100 mg/kg), at several times (0, 2, 4, 12 and 24 h) after LPS injection. Endotoxic shock decreased the levels of AA in the leukocytes from the three organs as well as the levels of GSH in axillary nodes and spleen cells while it increased the GSH levels in thymus and peritoneum. These results are in agreement with the oxidative stress and the altered function previously observed in those leukocytes, and they suggest that antioxidant administration may be useful for the treatment of endotoxic shock and other oxidative stress situations with altered immunological responses.