Rationale and timeliness for IL-1beta-targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation.

摘要

Ischemia-reperfusion injury (IRI) involving allograft transplantation and procured organs may in part be induced by stimulation of a newly described innate pro-inflammatory immune system (i.e., NALP-3-inflammasome), which can cause secretion of IL-1beta and subsequent neutrophilic inflammation. Ischemia and/or hypoxia/anoxia can induce anaerobic metabolism with metabolic acidosis and subsequent development of danger signals known to stimulate IL-1beta secretion from the NALP-3 inflammasome. Observations from IRI studies and hereditary auto-inflammatory syndromes with NALP-3 inflammasome mutations suggest that IL-1beta secretion can induce robust neutrophilic inflammation that is responsive to IL-1beta targeted therapy. Based on these observations and data from transplantation studies, it may be timely to consider commercially available IL-1beta targeted biologic therapy to improve allograft tolerance and viability of procured organs.