E. Snella et al., RELATIONSHIP OF AGING AND CYTOKINES TO THE IMMUNOMODULATION BY DELTA-9-TETRAHYDROCANNABINOL ON MURINE LYMPHOID-CELLS, International journal of immunopharmacology, 17(12), 1995, pp. 1045-1054
The effect of delta 9-tetrahydrocannabinol, the major psychoactive com
ponent of marijuana, was investigated utilizing lymphoid cells from 2-
week, 2-month, and 18-month-old mice. Previous studies have shown a di
fferential modulation by THC related to age such that cells from adult
mice could be up-regulated by THC when stimulated by their CD3 recept
or. Cells from 2-week-old and 18-month-old mice were resistant to this
THC-mediated enhancement. This paper questioned whether these resista
nt cells could be up-regulated by either addition or removal of cytoki
nes 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 o
f 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 fa
ct, suppressive. Addition of IL-2 or supernatants from adult cells did
lead to a modified THC-induced up-regulation of proliferation in cell
s 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 cultur
e. These results demonstrate a difference in immune response to THC re
lated 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 im
munoenhancing 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.