Cannabis interacts with the immune system, but can it help reduce organ transplant rejection?
Recent years have seen the increased use of cannabinoids as anti-inflammatory medicine due to their efficacy in treating many immune-mediated diseases, including multiple sclerosis, autoimmune hepatitis, and rheumatoid arthritis. This is exciting because, not only can such properties be exploited for inflammatory disease, but also for conditions where autoimmunity modulation plays a role, such as organ transplant rejection.
The Immune System is the Enemy of Transplants
The immune system is one of the most important physiological tools of an organism. It offers protection against foreign substances, called antigens, so that we don’t fall ill every time we come in contact with something that’s new to us. On the other side, the immune system can be one’s biggest enemy, especially when the individual is a transplant patient.
When an organ or tissue is exchanged between genetically non-identical individuals, there is a risk that the recipient will develop immune response aimed at destroying the transplant, leading to rejection. This is the reason why transplant patients must keep up a regime of immunosuppressants following a transplant.
While the use of immunosuppressants has significantly reduced the rate of transplant rejection, it is a “double edge sword” because it also makes the tissue or organ recipient more vulnerable to infection and cancer. Reducing the incidence of these deleterious side effects is the main goal of many researchers in the transplant medicine field.
Can Cannabis Suppress Immune Response to Prevent Transplant Rejection?
Recent studies have described that CB2 receptor activation has immunosuppressive effects. Interestingly, and perhaps even more importantly, CB2 is selectively enriched on the surface of immune cells. This means that CB2 agonists, like THC, are likely to target these particular cells. In fact, CBD has been shown to kill mouse immune cells called T lymphocytes. Likewise, THC has been shown to have the same effect when administered in mouse models of disease, targeting immune cell populations such as T cells, B cells, dendritic cells and macrophages.
The immunomodulatory function of cannabinoids is not only observed by their ability to kill immune cells, but also by their ability to stimulate immune cells to produce specific kinds of molecules.
There are 2 kinds of molecules, called cytokines, that immune cells can produce: pro-inflammatory (Th1) and anti-inflammatory (Th2) which can either amp up the inflammation (pro-inflammatory) or calm it down (anti-inflammatory).
THC and CBD have been shown to suppress the pro-inflammatory Th1 cytokine production in favour of Th2 cytokines in mouse lung cells , human T and B cells and in mouse model of tissue injury after a heart attack . This is important because it is believed that transplant rejection is mediated by the Th1-produced cytokines, and therefore it is tempting to speculate that suppression of the Th1 response by cannabinoids will likely decrease the odds of transplant rejection.
Cannabis and Trans-Endothelial Migration
Another piece of the puzzle for a successful transplant resides in the cells that line the blood vessels, called endothelial cells. Endothelial cells are the gate keepers between the blood and tissues. This means they are the point of entry for the immune cells into the transplanted organ.
The crucial action of endothelial cells to “let the immune cells pass through” to the transplanted organ can be interfered with by cannabinoids. It has recently been shown that in human coronary artery endothelial cells, activation of CB1 and CB2 receptors significantly reduced the expression of molecules that attract the immune cells (called chemoattractant) and let them pass (a process called transendothelial migration).
Cannabinoids Have Promise for Transplant Recipients
When the transplanted organ is protected from attack by the host’s immune cells, there is a better chance of establishing the organ in its new body. Currently, there are no studies evaluating the impact of cannabinoids on the ability of transplant to establish new vessels. Nevertheless, the plethora of data describing that cannabinoids have immunomodulatory and anti-inflammatory (via suppression of Th1 cytokine production) effects and that they can modulate endothelial cell function suggest that they are likely to create an environment in which the transplanted organ is more likely to get accepted. It is definitely worth investigating.