title: Interleukin-1beta targeted therapy in severe persistent asthma (SPA) and chronic obstructive pulmonary disease (COPD): proposed similarities between biphasic pathobiology of SPA/COPD and ischemia-reperfusion injury.
abstract: The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA and COPD, which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1beta secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1beta targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.
authors.affiliation: Pediatrics and Allergy-Clinical Immunology, University of Colorado Health Sciences Center, Denver, CO, USA. aw@aacmt.com
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wanderer
mesh_terms: D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002131:Calcium Pyrophosphate / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015427:Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D002131:Calcium Pyrophosphate