7.4 n&v 707 MH

cells collected from the lungs of marijuana smokers produce lower than normal amounts of several cytokines and fail to produce nitric oxide (another intermediary in the immune system), severely limiting their ability to kill bacteria. Steffens and colleagues set the stage for their work by demonstrating that immune cells expressing CB2 receptors infiltrate atherosclerotic plaques in humans and in a strain of mice that is used to study atherosclerosis (ApoE mice). In this mouse model, the animals develop progressive narrowing of their arteries as lipids and inflammatory cells called macrophages enter the walls of their blood vessels and produce plaques. When low doses of THC (1 mg per kg body weight per day) were added to their diet, the progression of atherosclerosis was markedly slowed. Mice that were fed THC still had elevated levels of serum lipids but had fewer plaque-infiltrating macrophages when compared with controls, suggesting an effect on immune function. The authors go on to substantiate the immunosuppressive properties of THC on the migration, infiltration and function of immune cells in this model. Spleen cells collected from THC-treated mice responded poorly to stimulation in vitro, showing limited proliferation and impaired production of interferon, a cytokine involved in atherosclerosis. Macrophages harvested from THC-treated animals expressed little of the messenger RNA encoding the CCR2 receptor protein,and were poorly responsive to the CCR2 ligand, MCP-1. Both CCR2 and MCP-1 are involved in the migration of macrophages and have roles in atherosclerosis. These effects were blocked when mice were pre-treated with a selective antagonist to the CB2 receptor or when macrophages were collected from mice that lack functional CB2 receptors. Using live vascular microscopy, the authors observed that adhesion of immune cells to the internal surface of blood vessels was considerably reduced in mice that were fed THC. Again, this effect was blocked by pre-treating the animals with a CB2 antagonist. The protective effects of THC occurred at very low doses, producing blood THC levels well below the range usually associated with activation of CB1 receptors in the brain. The authors conclude that low doses of THC, or perhaps selective CB2 ligands, should be further investigated for their possible use in treating human atherosclerosis. The findings by Steffens et al. are striking, but they should not be taken to mean that smoking marijuana is beneficial for the heart. The dose-response curve to THC in this study was very narrow and U-shaped, with higher and lower concentrations failing to produce protective effects. It would be difficult to achieve such specific concentrations news and views