Studies of immunomodulating actions of carotenoids. I. Effects ofβ‐carotene and astaxanthin on murine lymphocyte functions and cell surface marker expression inin vitroculture system

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Abstract
The immunomodulating effects of carotenoids (β‐carotene and astaxanthin) on mouse lymphocytes were studied in in vitro culture system by use of assay for mitogen responses of spleen cells, thymocyte proliferation, interleukin 2 production, and antibody (Ab) production in vitro in response to sheep red blood cells. Changes of cell surface markers on spleen lymphocytes including la antigen (Ag), surface immunoglobulin, B220, and Thy‐1 Ag were also examined. At a concentration of 10‐8 M, carotenoids did not show any significant effect on mitogen responses (phytohemagglutinin P and concanavalin A) on murine spleen cells, irrespective of the concentrations of mitogens used. Interleukin 2 production by murine spleen cells was not significantly altered by carotenoids in the culture media (10‐7 to 10‐9 M). [3H]thymidine incorporation by B6 thymocytes was somewhat enhanced in the presence of astaxanthin or β‐carotene when cultured in the concentration of l06/ml. At higher concentrations of cells (5 × 106/ml), such an effect was not observed. In assays of in vitro Ab production in response to sheep red blood cells, B6 spleen cells produced significantly more Ab‐forming cells (plaque‐forming cells, immunoglobulins M and G) in the presence of astaxanthin (> 10‐8 M) but not β‐carotene. Expression of Ia Ag seemed to be moderately enhanced on both Thy‐1+ and Thy‐1‐ spleen cells in the presence of astaxanthin (> 10‐9 M) but not β‐carotene. The expression of Thy‐1 and surface immunoglobulin seemed unchanged with the treatment of these carotenoids. These results indicate that immunomodulating actions of carotenoids are not necessarily related to provitamin A activity, because astaxanthin, which does not have provitamin A activity, showed more significant effects in these bioassays and also indicate that such actions of carotenoid demonstrated in this study may be difficult to explain only by its oxygen‐quenching capacity.