Efeito do uso de canabidiol na doença do enxerto versus hospedeiro em camundongos

Abstract

Bone-marrow transplant (BMT) is a curative therapy for several hematological diseases, tumors, cancers and even some autoimmune diseases. However, the main concern about BMT is that patients that undergo allogenic or semi-alogenic transplants might develop a secondary disease know as Graft versus host disease (GVHD), in with the bone marrow transplanted cells recognize antigenic disparities between donor and host, leading to an active immune response against the host organism. The incidence of GVHD in humans ranges from 30 to 60% (Martin et al., 2015) and, among those who develop this disease, the mortality rate is up to 50% (Barton-Burke, 2008). Currrently, the main treatment for GVHD is the permanent and unceasing usage of high doses of corticosteroids, that lead to immune suppression and increases the chances of tumor reoccurrence. Therefore, our goal was to evaluate the actions of CBD, a potent anti-inflammatory drug and main non-psychoactive component of Cannabis sativa, in a murine model of GVHD, induced by the transplant of bone marrow cells (1x107) and splenocytes (3x107), from C67BL-6j to Balb-c mice. The mice host were daily treated with CBD (30mg/Kg) or vehicle (5% Tween80) for seven days, starting on the day of the transplant, the mice were then euthanized and their tissues were collected for histopathological, ELISA and flow cytometry analyses. CBD not only lead to an increase in survival rates, but also reduced the levels of TNF-α, IFN-γ, CCL2, CCL3 and CCL5 in the intestines, also increasing the number of FoxP3+ lymphocytes. However, in the liver, the treatment with CBD lead to the reduction only of IFNγ and CCL3, but the number of FoxP3+ lymphocytes were not altered. Besides, CBD also did not affect the cytotoxic effect against tumor or graft-versus-tumor effect (GVL) and, in a study with CB1 and CB2 antagonists, CBD demonstrated to be partially dependent of CB2, but not CB1 cannabinoid receptor to promote an increased survival. Therefore, according to this data, CBD is a potential treatment for GVHD due to its immunomodulatory and the increased survival, related to CB2 cannabinoid receptor.