Age related immunomodulation in murine splenocytes induced by delta-9-tetrahydrocannabinol (THC)

The purpose of this study was to investigate the immunomodulatory effects of THC (delta-9-tetrahydrocannabinol) on spleen cells of young (2 week), adult (2 month) and old (15 and 24 month) mice. THC has been shown by many investigators to suppress various immune parameters in adults. Since immune capabilities are already diminished at either age extreme, it seemed relevant to investigate the effect of this drug with aging. It was found that when spleen cells were stimulated with concanavalin A (Con A), phytohemagglutinin (PHA) or anti-CD3 antibody, the magnitude of the proliferation was greatest in the adult and less at either age extreme. When Con A or PHA stimulated cells were treated with varying doses of THC, the proliferation of cells was suppressed with the general pattern of suppression similar at all ages. However, the absolute magnitude of the resultant suppression was greater in young and old mice. In contrast, when the cells were stimulated with anti-CD3 antibody and THC, both the pattern of the immunomodulation as well as the absolute effects differed with age of the mice. In this regard, anti-CD3 stimulation and low doses of THC stimulated lymphocyte proliferation in the adult mice. This combination was found to increase CD3 positive cells of the Ly2 subclass (effector/suppressor) in the adult. At either age extreme, the THC induced enhancement of proliferation was not as apparent. In addition, the cells from mice at either age extreme were more readily suppressed at 7 micrograms THC than were adult cells. It appears, therefore, that age is an important variable in terms of considering the effects of drugs of abuse.