title: Inflammatory profiling of peripheral arterial disease.
abstract: The progression of peripheral arterial disease (PAD) is poorly understood but may be caused by an underlying inflammatory dysfunction. This study therefore profiled interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, anticardiolipin, and anti-beta2-glycoprotein 1 antibody concentrations and characterized patients' inflammatory response in vitro. Patients were classified according to World Health Organization criteria and ankle-brachial pressure index into critical ischemics (n=20), stable claudicants (n=20), and controls (n=20). In vitro studies involved culturing whole blood with RPMI-1640 for 24hr with and without 1 microg/mL lipopolysaccharide and profiling cytokine production. Autoantibody levels were measured using enzyme-linked immunosorbent assays, while cytokine profiles were determined by multiplex immunoassay. Serum IL-6, IL-10, IL-13, and anti-beta2-glycoprotein 1 antibody levels were higher in PAD (p<0.05). In the case of IL-6 and anti-beta2-glycoprotein 1 antibody, levels reflected increasing disease severity (p<0.05). In vitro studies revealed that IL-8 and IL-13 secretory capacities were significantly higher in PAD after 6 hr. However, when these were standardized against patient leukocyte count, cytokine production profiles did not differ. PAD features an increased inflammatory burden irrespective of Th1:Th2 cytokine type; this is more pronounced with increasing disease severity. However, the inflammatory hyperresponsiveness of cultured whole blood from PAD patients probably relates to associated leukocytosis, rather than being attributable to an inherent inflammatory dysfunction.
authors.affiliation: Leeds Vascular Institute, Leeds General Infirmary, Leeds, UK. drchaparala@hotmail.com
authors.forename: Ramakrishna P C
authors.initials: RP
authors.lastname: Chaparala
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Orsi
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Lindsey
authors.forename: Raman S
authors.initials: RS
authors.lastname: Girn
authors.forename: Shervanthi
authors.initials: S
authors.lastname: Homer-Vanniasinkam
mesh_terms: D000368:Aged; D000842:Ankle / Q000098:blood supply; D017153:Antibodies, Anticardiolipin / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001794:Blood Pressure; D001916:Brachial Artery / Q000503:physiopathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007378:Interleukins / Q000097:blood; D007383:Intermittent Claudication / Q000276:immunology* / Q000503:physiopathology; D007511:Ischemia / Q000276:immunology* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000276:immunology; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D012720:Severity of Illness Index; D053482:beta 2-Glycoprotein I / Q000276:immunology
chemical_list: D017153:Antibodies, Anticardiolipin; D001323:Autoantibodies; D018836:Inflammation Mediators; D007378:Interleukins; D008070:Lipopolysaccharides; D053482:beta 2-Glycoprotein I