Uso de nanocompostos como potencial estratégia farmacológica no controle da resposta inflamatória associada à doença do enxerto versus hospedeiro (GVHD) induzida em camundongos

Abstract

Graft-versus-host disease (GVHD) is the greatest complication limiting the clinical utility of allogeneic hematopoietic stem cell transplantation (HSCT), in which lymphocytes of donors (graft) are activated in response to host antigen. This elicits a cytokine cascade involving cytokine/chemokine production resulting in enhanced expression of major histocompatibility complex (MHC) and costimulatory molecules on tissue antigen-presenting cells (APCs). Donor T cells subsequently become activated through recognition of host alloantigens and differentiate into effector T cells that recruit other cell types and lead to local inflammation and target tissue destruction. The recruitment of leukocytes to target organs is controlled by complex interaction between adhesion molecule, production of chemokine/cytokine and reactive oxygen species (ROS). Fullerols are nanocomposites with closed symmetry structure and anti-inflammatory and anti-oxidant properties that work as free radical scavengers. So, this study aimed to verify the effects of fullerol in a pathogenesis and development of GVHD using a model of adoptive transfer of splenocytes from C57BL/6J mice to B6D2F1 mice. The treatment with fullerol reduced mortality and severity of clinical signs of GVHD. This protection was associated with reduced production of ROS in liver and spleen. Further, the treatment with fullerol reduced production of pro-inflammatory cytokines and chemokines (IFN, TNF, CCL2, CCL3, CCL5), leukocytes accumulation in liver and provide lesser hepatic injury and bacterial translocation after twenty days of disease. Similarly, treatment with apocynin, which was given to WT transplanted mice, also resulted in reduced mortality and less weight loss and clinical scores. We suggest that strategies aimed at blocking the action of ROS may be useful in the treatment of GVHD. Then, in this study the fullerol was effective in reducing GVHD inflammatory response associated with GVHD in murines an could be relevant therapeutic strategies for this disease.