Ischemic-reperfusion syndromes: biochemical and immunologic rationale for IL-1 targeted therapy.
Ischemic-reperfusion injury (IRI) can affect many organ systems. Examples include strokes, coronary occlusion, accidental hypothermia, compartment syndrome and neonatal hypoxia. To date no mechanism has been fully accepted to explain acute inflammation associated with IRI. There is circumstantial evidence from animal and human ex-vivo cardiac experiments to support the hypothesis that acute inflammation associated with IRI is in part caused by IL-1 beta and/or IL-1 alpha secretion. Danger signal formation, such as uric acid/calcium pyrophosphate crystallization and other cellular stresses, may occur in IRI. These in turn may stimulate innate immune pathways (i.e. cryopyrin-inflammasome; and/ or toll-like receptors 2 and 4) to secrete IL-1 beta. Most IL-1 targeted therapy studies have focused on chronic human diseases and hopefully this discussion will create a framework to encourage use of this therapy in acute inflammation associated with IRI.
Wanderer
Alan A
AA
Pediatrics, University of Colorado Health Sciences Center, 2055 North 22nd Avenue, Bozeman, MT 59718, USA. aw@aacmt.com
D000818:Animals; D002131:Calcium Pyrophosphate / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D007511:Ischemia / Q000276:immunology* / Q000503:physiopathology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D051193:Toll-Like Receptors / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D014527:Uric Acid; D002131:Calcium Pyrophosphate