DELTA(9)-TETRAHYDROCANNABINOL (THC) MODULATES IL-1 BIOACTIVITY IN HUMAN-HUMAN MONOCYTE-MACROPHAGE CELL-LINES

We have previously observed that DELTA9-tetrahydrocannabinol (THC), th e major psychoactive component of marijuana, increased supernatant int erleukin-1 (IL-1) bioactivity in cultures of mouse resident peritoneal macrophages stimulated with lipopolysaccharide (LPS). In this study, experiments were performed to determine whether THC treatment similarl y affected phagocytes of human origin. The results showed that THC inc reased the levels of supernatant IL-1 bioactivity of two human monocyt ic cell lines, but only if the cells were differentiated with phorbol myristate acetate. Undifferentiated cells displayed decreased IL-1 bio activity in response to THC. However, under conditions in which THC au gmented supernatant IL-1 bioactivity from THP-1 cells, ELISA studies s howed that the levels of IL-1alpha and IL-1beta were unchanged and dec reased, respectively. Furthermore, supernatant interleukin-6 (IL-6) le vels were decreased, but tumor necrosis factor (TNF-alpha) levels were increased by THC treatment. These results show that THC treatment mod ulates cytokine production and/or release by mouse and human macrophag es and the drug effects on IL-1-like bioactivity in the supernatants o f the human THP-1 cells are due to increased levels of other cytokines , such as TNF-alpha, rather than IL-1 itself.