Efeito de fração proteolítica do látex de Vasconcellea cundinamarcensis na resposta inflamatória associada à doença do Enxerto-Contra-Hospedeiro (DECH) Murina

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic strategy widely used in the treatment of hematological and non-hematological diseases. However, its clinical success is often limited by the development of graft-versus-host disease (GVHD), an immune-mediated complication that occurs when graft T lymphocytes recognize host antigens as non-self, promoting cell activation, proliferation and infiltration in target organs such as the intestine, liver and skin. Approximately 40% of patients are resistant to conventional corticosteroid therapy, representing a significant challenge for the management of GVHD and directly impacting the efficacy of HSCT. Given this scenario, we investigated the therapeutic potential of the proteolytic fraction P1G10, derived from the latex of Vasconcella cundinamarcensis, which has anti-inflammatory and anti-tumor properties described in various experimental models. Plant proteases such as P1G10 have been widely studied for their ability to modulate exacerbated immune responses. Using a murine model of acute GVHD, induced by transplanting bone marrow cells and splenocytes from Balb/c mice into C57BL/6J recipients, we evaluated the effects of P1G10, administered at a dose of 0.3 mg/kg, on the exacerbated inflammatory response characteristic of GVHD. Mice that received bone marrow cells and splenocytes were used as a control group who did not develop the disease. Treatment with P1G10 reduced TNF-α levels in the intestine and IFN-γ levels in the intestine, liver and serum, as well as decreasing the expression of the inflammatory chemokines CCL2 and CCL3 in the intestine and serum. Flow cytometry analysis, carried out on the spleen, intestine and liver, revealed distinct modulation in the populations of CD4⁺ T cells, CD8⁺ T cells, regulatory T cells (Tregs) and macrophages, indicating an organ-specific immunoregulatory action. In addition, P1G10 significantly preserved the integrity of the intestinal barrier, preventing bacterial translocation and maintaining the goblet cell population in the colon. In the experimental graft- versus-leukemia (GVL) model, P1G10 did not interfere with the anti-tumor activity of the graft, demonstrating its therapeutic selectivity. These results position P1G10 as a promising approach for the treatment of refractory GVHD, combining immunomodulatory effects, protection of the intestinal mucosa and maintenance of antileukemic action