Mechanisms of hemorrhagic cystitis

Abstract

The vast majority of cases of infectious cystitis are easily treated, and most patients have no long-term complications. However, hemorrhagic cystitis is a potentially deadly complication associated with pelvic radiation therapy, chemotherapy, and stem-cell transplant therapy. The focus of current understanding, and hence therapy, is directed toward urothelial cell death. However, the primary functional ramification of inflammatory bladder disease is the loss of compliance due to muscular expansion. Recent studies on smooth muscle response in models of bladder inflammation demonstrate a process of pyroptotic cell death that potentiates further muscle hyperplasia. These findings may support alternative interventions for subjects with hemorrhagic cystitis refractive to current therapy.

Keywords: Bladder inflammation; pyroptosis; radiation cystitis.

Figure 1

A model of inflammasome formation in urinary bladder muscle mediated by ROS production and oxidative damage in mitochondria. Activation of NLRP3 allows inflammasome complex formation and bioactivation of NF-κB mediated IL-1β expression via cleavage of caspase1. IL-1β secretion by a bladder smooth muscle cell undergoing pyroptotic cell death can support the proliferation of the remaining muscle cells by activation of any number of growth factors including IGF1. There are a few known inhibitors of the multiple steps process of bladder muscular expansion.