Anti-Inflammatory Resveratrol Protects Mice From Early Mortality After Haematopoietic Stem Cell Transplantation

Abstract

The occurrence of inflammation subsequent to haematopoietic stem cell transplantation is associated with an elevated risk of transplant-related mortality (TRM). However, the duration of inflammation and the potential efficacy of anti-inflammatory agents in reducing TRM remain uncertain. We performed a comprehensive investigation to examine the post-transplantation alterations of inflammatory mediators and to ascertain the correlation between inflammation level and TRM through the neutrophil–lymphocyte ratio, ELISAs and cytometric bead array. The findings revealed that the 30-day interval following transplantation is characterised by the most pronounced inflammatory response in both human and murine subjects, thereby elevating the risk of TRM. The inflammation is primarily caused by myeloid bias during haematopoietic reconstitution, which is a commonly overlooked aspect in clinical transplantation, additionally, a lesser extent of irradiation-induced injury. The administration of the anti-inflammatory agent resveratrol has the potential to reduce systemic inflammation and TRM by suppressing the NOD-like receptor signalling pathway and slowing down granulocyte implantation in HSCT mice. This approach did not impair the differentiation potential of haematopoietic stem cells. These findings demonstrate that the 30-day post-transplant period represents an opportunity to facilitate HSCT colonisation, mitigate transplant-related adverse effects, and potentially reap the benefits of anti-inflammatory treatments.