Search

Objective: A human intervention trial was conducted to determine the effects of consumption of carotenoid-rich vegetables on levels of retinol (ROL) and the active vitamin A metabolite all-trans retinoic acid (ATRA)., Methods: The study was divided into four periods, each lasting 2 wk: weeks 1-2, a low carotenoid period; weeks 3-4, daily consumption of 330 mL of tomato juice; weeks 5-6, 330 mL of carrot juice daily; and weeks 7-8, 10 g of dried spinach powder daily. ROL and ATRA concentrations were measured after each 2-wk study period., Results and Conclusion: This study shows that consumption of carrot juice containing high concentrations of the pro-vitamin A carotenoid beta-carotene results in slightly, non-significantly increased plasma ROL concentrations and strong, significantly increased (almost double, from 1.2 +/- 0.3 to 2.0 +/- 0.31 ng/mL) plasma concentrations of ATRA, whereas consumption of tomato juice and spinach powder results in no significant alteration in concentrations of plasma ROL and ATRA.

Polyphenolic compounds exert a variety of physiological effects in vitro including antioxidative, immunomodulatory and antigenotoxic effects. In a randomized crossover study in healthy men on a low-polyphenol diet, we determined the effects of 2 polyphenol-rich juices (330 ml/d) supplemented for 2 weeks on bioavailability of polyphenols, markers of antioxidative and immune status, and reduction of DNA damage. Juices provided 236 mg (A) and 226 mg (B) polyphenols with cyanidin glycosides (A) and epigallocatechin gallate (B) as major polyphenolic ingredients. There was no accumulation of plasma polyphenols after two weeks of juice supplementation. In contrast, plasma malondialdehyde decreased with time during juice interventions. Moreover, juice consumption also increased lymphocyte proliferative responsiveness, with no difference between the two juices. Interleukin-2 secretion by activated lymphocytes and the lytic activity of natural killer cells were significantly increased by both juices. Juice intervention had no effect on single DNA strand breaks, but significantly reduced oxidative DNA damage in lymphocytes. A time-delay was observed between the intake of fruit juice and the reduction of oxidative DNA damage and the increase in interleukin-2 secretion. We conclude that consumption of either juice enhanced antioxidant status, reduced oxidative DNA damage and stimulated immune cell functions. However, fruit juice consumption for 2 weeks did not result in elevated plasma polyphenols in subjects after overnight fasting. Further studies should focus on the time-delay between juice intake and changes in measured physiological functions, as well as on active polyphenolic metabolites mediating the observed effects.

The objective of this study was to determine if chronic ethanol consumption could modify cell populations in the Peyer's patches (PP), which could favor pathogenic or opportunistic infections in mice, as seen in chronic alcohol addicts. Young C57BL/6 mice receiving the Lieber-DeCarli diet (36% of calories as ethanol) for 5 weeks presented a significant decrease in the total number of cells in the PP. Mature FVB mice receiving the Lieber-DeCarli diet for 19 weeks presented a highly significant decrease in the total number of cells and in the absolute number of T and B cells in the PP. Young C57BL/6 mice receiving the 100% NRC (30% ethanol) or the 60% NRC (30% ethanol) diets for 7 weeks presented alterations in the T and B cell phenotype comparable with the alterations observed in mice receiving the Lieber-DeCarli diet for 19 weeks. As less alcohol for a shorter time caused similar changes to those seen with a highly micronutrient enriched diet with more alcohol for a longer consumption period, micronutrient supplementation may overcome some immune damage found in animal models of alcoholism. Our data indicated that ethanol administration altered the mucosal immune system at the level of the PP, the site for antigen presentation and induction of a mucosal immune response.

Severe infections in intravenous drug abusers could be the consequence of morphine-induced damage on the immune system. To evaluate the long-term effect of in vivo morphine administration on the immune system we developed an experimental model where we studied the combined effects of morphine treatment and protein malnutrition. We treated protein-undernourished mice daily for 11 weeks with increasing doses of morphine. Morphine treatment produced a decrease in body weight and spleen cell number. The changes observed were partially independent of the nutritional status of the host. Saline-injected mice showed a decrease in the percentage of Thy 1+ cells in the spleen. Morphine treatment induced a decrease in the total number of cells and therefore in the absolute number of T-(Thy 1, CD4, CD8), B- and Mac 1+ (macrophages) cells in protein-undernourished mice. Saline-injected mice showed a decrease in the percentage of Thy 1+ cells and an increase in the percentage of B- and Ia(+)-cells in the spleen. We conclude that morphine altered the immune system by down-regulating splenocyte proliferation. We also studied the effects of i.p. administered morphine on expression of thymocyte phenotype in well-nourished and protein-undernourished mice. In well-nourished mice, morphine treatment reduced the number of Thy 1+, CD4+ and CD8+ cells per thymus to 30% of that found in untreated mice and to 40% of the cells in those saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous heroin abusers suffer a great variety of infections, including AIDS (acquired immune deficiency syndrome). We developed an experimental mouse model to evaluate the long-term effect of in vivo morphine administration during retrovirus-induced immune dysfunction. Mice were treated daily for 11 weeks with increasing doses of morphine. Morphine treatment produced a decrease in body weight and spleen cell number. Murine retrovirus infection provoked an increase in body weight due to enlargement of lymphoid organs, and an increase in the percentage and absolute number of CD4+ and Mac 1+ cells. Interestingly, retrovirus-infected mice that were also morphine-treated did not show the increase in the relative proportion of Mac 1+ cells. Moreover, under the experimental conditions of protein-malnutrition and morphine treatment potentiation of immune dysfunction by murine retrovirus infection was investigated. Retrovirus infection-induced splenocyte proliferation was partially regulated by morphine treatment. Splenocytes from retrovirus-infected mice presented a higher percentage of IL-2R+ cells and, lower levels of sIL-2R in splenocyte supernatants. Mitogen-stimulated splenocytes had a lower production of interferon-gamma as well as an increase in the secretion of tumor necrosis factor-alpha. Thus morphine altered the immune system by down-regulating splenocyte proliferation, because retrovirus infection-induced splenocyte proliferation was partially regulated by morphine treatment. We also evaluated the effects of joint murine retrovirus infection and protein undernutrition on the thymus cell subsets. Retrovirus infection was associated with a decrease in the absolute number of Thy 1+, CD4+ and CD8+ cells per thymus with the CD8+ cell subset being the most affected. Moreover, retrovirus-infected mice presented a dramatic decrease in the percentage of double-positive (CD4+ CD8+) cells in the thymus as well as changes in its immunoarchitecture. While protein undernutrition alone did not produce further differences between infected versus non-infected, protein-undernourished, morphine treatment induced a greater decrease in thymocyte number than that seen in retrovirus- or morphine-treated animals alone.

Alcoholics have frequent bronchial and intestinal bacterial-associated infections compromising the mucosal-associated lymphoid tissues. Alcoholics also suffer undernutrition due to changes in their lifestyles. Thus, we studied the intestinal mucosa-associated lymphoid tissues using two types of diets in young and mature mice. The objective was to elucidate if ethanol consumption alters the T and B cell populations in the intestine, and if the alteration could be associated with the age and/or the nutritional status of the host. There was an increase in the number of CD8+ cells per field in the intestinal lamina propria (ILP) of young mice consuming ethanol, with no change in CD4+ and IgA+ cells in the ILP and CD4+ and CD8+ cells in the intestinal intraepithelium (IE). There was also an increase in the number of CD4+ and CD8+ cells in the ILP of well-nourished mature mice consuming ethanol, and an increase in the number of CD4+ cells in the ILP of undernourished mice. An increase in the number of CD8+ cells in the IE was also detected in the well-nourished group consuming ethanol. Therefore, we conclude that ethanol administration alters the intestinal mucosa-associated lymphoid tissue.

The effects of cocaine (0.1-100 micrograms/ml) were studied on interferon-gamma (IFN) secretion in Con A-stimulated splenocytes from young (4 months) and old (18 months) C57BL/6 mice. IFN secretion was significantly suppressed by cocaine in a concentration-dependent manner. Suppression was observed in splenocytes from both young and old mice. Splenocytes from young mice released higher amounts of IFN (23.40 +/- 1.47 ng/ml) than those from old mice (6.10 +/- 0.35 ng/ml) after 24 h in culture. The concentration of Con A used to stimulate IFN secretion significantly affected the suppressive effect of cocaine. Pretreatment of splenocytes with cocaine followed by culture in the absence of cocaine did not affect IFN secretion in old mice, while splenocytes from young mice showed a sustained depression in IFN release. This suggests that cocaine suppresses IFN release in vitro and the susceptibility to this inhibitory effect may be age related.

We investigated the in vitro effects of both psychoactive and nonpsychoactive marijuana components on leukocyte secretion of the immunoregulatory cytokines interleukin-1 alpha (IL-1), tumor necrosis factor alpha (TNF), interferon-gamma (IFN) and interleukin-2 (IL-2). Psychoactive delta-9-tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD) were added to cultures of mitogen-activated human peripheral blood mononuclear cells (PBMC) and the concentrations of IL-1, TNF, IFN and IL-2 in culture supernatants were measured by ELISA systems. Concentrations of THC and CBD, comparable to plasma levels found after smoking marijuana (10-100 ng/ml), increased the concentration of measurable IFN (139 and 68%), while high concentrations of both cannabinoids (5-20 micrograms/ml) completely blocked synthesis and/or release of this cytokine. CBD was also shown to decrease the measurable quantity of both IL-1 and TNF. In contrast to the effects on IFN, IL-1 and TNF, both cannabinoids, had no effect on IL-2 secretion. This report suggests that both psychoactive and nonpsychoactive components of marijuana are immunomodulating and can potentially alter cytokine secretion of human PBMC.