Healthy aged and young blood donors were investigated for the role of membrane lipid composition in the age-related increase in membrane microviscosity and decline of mitogen responsiveness. Membrane microviscosity was shown to correlate positively with membrane cholesterol/phospholipid molar ratios, which were significantly elevated in the elderly. A positive correlation also was confirmed between lymphocyte membrane microviscosity, which was measured using the probe 1,6-diphenyl 1,3,5-hexatriene, and phytohemagglutinin responsiveness of cells from the same donor. Using stepwise regression statistical analysis, the variables age, cholesterol, cholesterol/total phospholipid and phosphatidyl ethanolamine/phosphatidyl choline molar ratios were all shown to have a significant positive influence on membrane microviscosity, whereas total phospholipids had a negative effect. No statistically significant difference was seen in content of any single saturated or unsaturated fatty acid between young and old donors. After pooling, however, the proportion of all unsaturated fatty acids was significantly higher in cells from the elderly as a consequence of an increase of n-6 and n-3 polyunsaturated fatty acids. Changes in lipid composition and physical properties of lymphocyte plasma membranes may, therefore, be responsible (at least partially) for the diminution of immune reactivity in old age.

The whole-body inflammatory response produced by cardiopulmonary bypass is an important cause of perioperative morbidity after cardiac operations. This inflammatory response produces reactive oxygen species and other cytotoxic substances, such as the cytokines. The generation of reactive oxygen species might deplete principal antioxidant micronutrients, that is, vitamins C and E and the carotenoids, Therefore, we have investigated the time course of the plasma concentrations of vitamins C and E and the carotenoids in 18 patients undergoing coronary bypass operations after randomization for previous vitamin E supplementation (300 mg dl-a-acetyl-tocopherol 3 times daily for 4 weeks) or placebo. Supplementation with a-tocopherol doubled the lipid-standardized plasma vitamin E concentration to 63.7 ± 14.5~moljL when compared with that of the control subjects (31.2 ± 9.0~moljL) before the operation. The plasma concentrations of vitamin C (36.0 ± 19.0~mol/L and 44.0 ± 21.7 mol/L, respectively) and of the carotenoids were not statisticaUy different between the two groups at baseline. The absolute plasma concentrations of both vitamin E and the carotenoids decreased during and after cardiopulmonary bypass, but after correction for hemodilution the plasma concentrations of vitamin E and the carotenoids showed no decrease. The vitamin E concentrations in the erythrocytes did not change either. In contrast, the plasma concentration of vitamin C decreased in all subjects within 24 hours after the operation by roughly 70 %. Correction for hemodilution still revealed a significant decrease in plasma vitamin C that persisted in most patients up to 2 weeks. In conclusion, the vitamin E and the carotenoid plasma concentrations are of no major concern during and after cardiac operations. In contrast, the serious depletion of vitamin C may deteriorate the defense against reactive oxygen species-induced injury during cardiac operations.

Blood from 19 patients was examined for the essential antioxidants alpha-tocopherol and beta-carotene before, during, and after bone marrow transplantation (BMT). Marrow ablation and immunosuppression for BMT conditioning was achieved by treatment with high-dose chemotherapy, mostly combined with total body irradiation. All patients required total parenteral nutrition beginning 1 wk before BMT. After conditioning therapy the concentration of absolute and lipid-standardized alpha-tocopherol and beta-carotene in plasma decreased significantly, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early posttransplant organ toxicity.

The blood from 19 patients having bone marrow transplantation was examined for the essential antioxidants alpha-tocopherol and beta-carotene as well as lipid hydroperoxides before, at and after bone marrow transplantation (BMT). Conditioning therapy, preceding BMT in order to achieve marrow ablation and immunosuppression, consists of high-dose chemotherapy which is mostly combined with total body irradiation (TBI). In order to see a possible difference between patients with and without additional TBI, we divided the patients up into two groups; patients receiving TBI (RT+) and patients without TBI (RT-). All patients required total parenteral nutrition beginning one week prior to BMT. After conditioning therapy plasma levels of absolute and lipid-standardized alpha-tocopherol and beta-carotene decreased in both groups, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early post-transplant toxicity. Lipid hydroperoxides increase significantly in the group of patients with additional TBI, whereas the other group, receiving no additional TBI, showed no significant change. We suggest high-dose supplementation of essential antioxidants for patients undergoing BMT.

Decreased mitogen responsiveness of lymphocytes during aging correlates inversely with membrane microviscosity, which reflects an altered lipid composition. Therefore, we addressed the question, whether age-related alterations of lipid metabolism affect the switch in lipid composition during formation of blasts. Membrane lipids and fatty acids of peripheral blood lymphocytes from SENIEUR protocol compatible ("healthy") elderly donors (66-77 yr) and young controls (18-30 yr) were quantified after incubation with or without the mitogen phytohaemagglutinin. The blastic change in membrane lipid composition was different for young controls with respect to cholesterol, phosphatidylethanolamine, total phospholipids, as well as several fatty acids. Moreover, the age-related alterations in the switch of membrane lipids and fatty acids were significantly correlated with a decreased mitogen response. Thus, the alterations in membrane reorganization during blast formation of lymphocytes from the elderly point to a disturbed cellular lipid homeostasis with possible impact on the age-related reduction in immune function.