Key result
Anti-IL-6 mAb reduces fibrosis and preserves contractility in a mouse model of chronic cardiac rejection.
Why the study?
Does neutralizing anti-IL-6 mAb prevent hypertrophy, fibrosis, and deterioration of graft contractility in a mouse model of chronic cardiac allograft rejection?
Does neutralizing anti-IL-6 mAb prevent hypertrophy, fibrosis, and deterioration of graft contractility in a mouse model of chronic cardiac allograft rejection?
IL-6 neutralization prevents pathologic hypertrophy, fibrosis, and contractile dysfunction in a mouse model of chronic cardiac allograft rejection, identifying IL-6 as a potential therapeutic target.
IL-6 neutralization merits exploration in cardiac transplant patients; leaves open translation from murine models to clinical efficacy.
Chronic cardiac allograft rejection is the major barrier to long term graft survival. There is currently no effective treatment for chronic rejection except re-transplantation. Though neointimal development, fibrosis, and progressive deterioration of graft function are hallmarks of chronic rejection, the immunologic mechanisms driving this process are poorly understood. These experiments tested a functional role for IL-6 in chronic rejection by utilizing serial echocardiography to assess the progression of chronic rejection in vascularized mouse cardiac allografts. Cardiac allografts in mice transiently depleted of CD4+ cells that develop chronic rejection were compared with those receiving anti-CD40L therapy that do not develop chronic rejection. Echocardiography revealed the development of hypertrophy in grafts undergoing chronic rejection. Histologic analysis confirmed hypertrophy that coincided with graft fibrosis and elevated intragraft expression of IL-6. To elucidate the role of IL-6 in chronic rejection, cardiac allograft recipients depleted of CD4+ cells were treated with neutralizing anti-IL-6 mAb. IL-6 neutralization ameliorated cardiomyocyte hypertrophy, graft fibrosis, and prevented deterioration of graft contractility associated with chronic rejection. These observations reveal a new paradigm in which IL-6 drives development of pathologic hypertrophy and fibrosis in chronic cardiac allograft rejection and suggest that IL-6 could be a therapeutic target to prevent this disease.
No takes yet. Share an insight, caveat, or question.
Díaz et al. (2009) studied Chronic cardiac allograft rejection. Neutralizing anti-IL-6 mAb vs. Untreated chronic rejection model was evaluated on Cardiomyocyte hypertrophy, graft fibrosis, and graft contractility. Neutralizing anti-IL-6 mAb ameliorated cardiomyocyte hypertrophy, graft fibrosis, and prevented deterioration of graft contractility in a mouse model of chronic cardiac allograft rejection.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: