The Effect On The Cardiac Remodeling And Function In The Pressure-overloading Rats Of Systematic Immunomodulating Drugs

Accumulating evidence indicates that the inflammatory response to the stimuli may represent a common final pathogenic pathway in congestive heart failure (CHF) regardless of the initial events. Inflammatory cytokines including tumor necrosis factor (TNF-α) play a pathogenic role in CHF by influencing heart contractility, inducing hypertrophy, and promoting apoptosis or fibrosis, contributing to the continuous myocardial remodeling process. Many data showed that the activation of inflammatory cell was observed in serum and the infiltration of it in the myocardium in hypertrophy models. These studies indicate that the strategy of anti-inflammatory therapy may improve cardiac remodeling and delay the progression of CHF. But traditional cardiovascular drugs seem to have little influence on the overall cytokine network. The results from the placebo-controlled studies suggested that anti-TNFαtherapy in patients with CHF had no effect, or even adverse effect, on mortality and hospitalization. On the other hand, some data have suggested that the nonspecific down-regulation of inflammatory cytokines may improve cardiac performance. Accordingly, it is important to further precisely identify the essence of the immunopathogenesis in CHF in order to develop more effective immunomodulating drugs for this disorder.A number of studies showed that methotrexate (MTX) and triptolide (TP), as two systematic immunosuppressive drugs, can exert nonspecific anti-inflammation effects in many diseases by inhibiting the infiltration of inflammatory cells in pathologic tissue, the activation of transcription factor NF-κB, as well as the release of inflammatory medium. For example, it is effective in modulating cytokine expression and get net benefit in various...