Beneficial Effects of Sitostanol on the Attenuated Immune Function in Asthma Patients: Results of an In Vitro Approach

Abstract

BackgroundIn vitro and animal studies have suggested that plant sterols and stanols increase cytokine production by T-helper-1 cells. This may be beneficial for patient groups characterized by a T-helper-2 dominant immune response, e.g. asthma patients. (1) to evaluate whether sitostanol induces a T-helper-1 shift in peripheral blood mononuclear cells (PBMCs) from asthma patients, and (2) to unravel the role of regulatory T-cells in this respect.Methodology/Principal FindingsPBMCs from 10 asthma patients and 10 healthy subjects were isolated and incubated with 1.2 µM sitostanol, while stimulated with 5 µg/ml PHA. Similar amounts of cholesterol were used to determine whether effects were specific for plant stanols or for sterols in general. Changes in cytokine production were measured using antibody arrays and ELISAs. Changes in regulatory T-cell population size were measured by flow cytometry, using intracellular Foxp3 staining. Sitostanol increased production of IFNγ by 6.5% and IL-2 by 6.0% compared to cholesterol (p<0.01). No changes in IL-4 and IL-13 were found. Interestingly, this effect was only present in PBMCs from asthma patients. The number of Foxp3+ cells tended to increase and their activity, measured by IL-10 production, increased after sitostanol treatment in PBMCs from asthma patients compared to controls by 32.3% (p = 0.077) and 13.3% (p<0.05), respectively.Conclusions/SignificanceAltogether, the sitostanol-induced Thelper-1 shift in PBMCs from asthma patients and the stimulating effects of sitostanol on Treg cell numbers and activity indicate a possible novel approach for plant stanol ester enriched functional foods in the amelioration of asthmatic symptoms. Functional effects, however, require further evaluation.

IL-17 level in patients with acute myocardial infarction and its effect on lipid profile

“…This finding is disagreement with results from previous studies which reports that IL-17 expression is up regulated under hypercholesterolemia conditions [22][23][24]. Another study show that cholesterol incubation significantly increases IL-17A production, which is consistent with findings in mice that a high-fat diet leads to increased IL-17A production [25]. Also, IL-17A Ab-treated mice have reduced atherosclerotic lesions in the presence of unchanged serum cholesterol and HDL/LDL ratio, therefore IL-17A is unlikely to affect atherogenesis via changes in hyperlipidemia or production of oxLDL Abs [15].…”

An acute intake of plant stanol esters alters immune-related pathways in the jejunum of healthy volunteers

“…However, immune-related pathways were down-regulated in the jejunum. This extends our earlier in vitro finding that sitostanol may exert immunomodulatory effects in subjects with a disturbed T-cell response ( 10 ) . However, the present study population had no known immune disorders.…”

“…We have already suggested that plant sterols and stanols influence immune function, when the immune response is disturbed. Brüll et al ( 10 ) showed that plant stanols induced a shift towards T helper 1 cells (Th1) in isolated human peripheral blood mononuclear cells from asthma patients. Furthermore, the number of Treg cells, which are important for maintaining the Th1/Th2 (T helper 2 cell) balance, tended to increase, whereas the activity of Treg cells increased significantly.…”

“…Furthermore, the number of Treg cells, which are important for maintaining the Th1/Th2 (T helper 2 cell) balance, tended to increase, whereas the activity of Treg cells increased significantly. These ex vivo changes may be specific for a situation of skewed T-cell behaviour, as they were not observed in peripheral blood mononuclear cells from healthy subjects characterised by a balanced Th1/Th2 response ( 10 ) . In vivo , Calpe-Berdiel et al ( 28 ) showed that administration of 2 % phytosterols increased the Th1:Th2 ratio in mice treated with turpentine in order to induce an acute, aseptic inflammation model.…”

“…The studies described so far have suggested that the plant stanol/sterol-induced Th1 or Th2 response depends on the direction of the disturbed Th1/Th2 balance. Restoration of this imbalance is probably the result of alterations in the number and activity of Treg cells ( 10 ) . In other words, when Th2 cells are overactivated, the activation of Treg cells restores the balance by stimulating the activity of Th1 cells, which via feedback mechanisms results in the dampening of Th2 cells ( 29 ) .…”