Supply of R-α-lipoic acid to glutamine-fed mice influences the number of B cells and tissue glutathione levels during endotoxemia

An overwhelming production of reactive oxygen species concomitant with a decreased antioxidative capacity plays an important role in the dysregulation of the immune system of critically ill patients. The purpose of this study was to assess the influence of a combined oral supply of the antioxidant R-α-lipoic acid (LA) and glutamine (GLN) on the immunity of endotoxemic mice with a special focus on tissue glutathione levels.

Female Balb/c mice were fed diets enriched with GLN (3g/100kcal), LA (0.74mg/100kcal), a combination of GLN and LA or an isocaloric and isonitrogenic control diet for 10 days. On day 7, the mice were challenged intraperitoneally with 25µg LPS. Seventy-two hours later, the number and phenotype of lymphocytes in Peyer's patches (PPs) and spleen of endotoxemic mice were measured by flow cytometry. Additionally, glutathione levels were determined in the small intestine, spleen and lung.

In PPs of endotoxemic mice only the combined supply of GLN and LA significantly increased total cell yield from 5.7±0.5 to 7.2±0.7×10⁶ cells (p<0.01). B cells were enhanced from 3.0±0.6 to 4.2±0.7×10⁶ cells (p<0.001), whereas the number of T cells remained unchanged. In the spleen, LA as well as a combined oral supply of GLN and LA increased total cell yield from 80.7±11.6 to 94.7±7.9×10⁶ cells (p<0.05) in LA-fed mice and to 98.7±6.6×10⁶ cells (p<0.01) in GLN + LA-fed mice, again predominantly due to an elevated number of B-cells. The glutathione content of the small intestine was elevated by feeding LA alone (duodenum: + 36%, p<0.01 and ileum: + 22%, p<0.05), whereas in lung and spleen GLN plus LA was most effective (spleen: + 34%, p<0.05 and lung: + 47%, p<0.05).

The combined supply of LA and GLN may combat secondary infections by enhancing systemic and intestinal B-lymphocytes. Moreover, LA and GLN act synergistically on glutathione metabolism, thereby serving as an interesting approach for the support of immuno-compromised patients.