Relationship of aging and cytokines to the immunomodulation by delta-9-tetrahydrocannabinol on murine lymphoid cells.

The effect of delta 9-tetrahydrocannabinol, the major psychoactive component of marijuana, was investigated utilizing lymphoid cells from 2-week, 2-month, and 18-month-old mice. Previous studies have shown a differential modulation by THC related to age such that cells from adult mice could be up-regulated by THC when stimulated by their CD3 receptor. Cells from 2-week-old and 18-month-old mice were resistant to this THC-mediated enhancement. This paper questioned whether these resistant cells could be up-regulated by either addition or removal of cytokines or by exposure to supernatants derived from adult cells. IL-1, IL-4, and IL-6 modified cell proliferation in general, and their effects had some age-related differences, but these actions were independent of THC. In contrast, the THC-induced enhancement appeared to be related in part to IL-2 levels in the adult cell cultures such that when IL-2 was removed, not only did up-regulation not occur, but THC was, in fact, suppressive. Addition of IL-2 or supernatants from adult cells did lead to a modified THC-induced up-regulation of proliferation in cells from adult or 2-week-old mice. Cells from 18-month-old mice remained resistant to this modulation by THC. This did not represent a general anergy of these older cells since they did proliferate well in culture. These results demonstrate a difference in immune response to THC related to the age of the mice which correlates at least in part to IL-2 levels in 2-week-old and young adult mice. THC modulation, whether immunoenhancing or suppressing, appears to be influenced by the presence of other cell stimulators such as cytokines, and is sensitive to the timing of THC exposure relative to such stimuli.