title: Rationale and timeliness for IL-1beta-targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation.
abstract: 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.
authors.affiliation: Allergy & Clinical Immunology, University of Colorado Health Sciences Center, Aurora, CO, USA. aw@aacmt.com
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wanderer
mesh_terms: D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D016377:Organ Transplantation / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D053583:Interleukin-1beta