title: Systemic inflammation and cell activation reflects morbidity in chronic heart failure.
abstract: Chronic heart failure (CHF) leads to complex effects distant from the heart. As these changes may be reflected in the balance of systemic inflammatory and fibrotic immunomodulators we measured these potential biomarkers in ambulatory CHF patients. Using the New York Heart Association (NYHA; levels II-IV) functional classification, 30 CHF patients were compared with 21 age and gender matched controls. Peripheral blood levels of regulatory cytokines (TNF-α, TGF-β, KGF, IL-8, IL-10 and IL-12) and markers of cellular activation (CD11b, CD16, CD18, CD34, HLADR, CXCR1 and CCR5) were analysed by ELISA and flow cytometry, respectively. NYHA classification, which reflected increasing pulmonary microvascular pressure (E:E') but not ejection fraction, was positively associated with TGF-β and IL-10 (p≤0.03). Similarly, monocytes, as well as cell surface expression of the neutrophil adhesion molecule CD11b, and the macrophage complement receptor complex (CD11b/CD18), were increased in CHF patients (p≤0.03), while the chemokine receptor CXCR1 was decreased on cells of CHF patients. Twenty month follow-up of CHF subjects identified monocyte number as a powerful prognostic factor for cardio-pulmonary adverse events (p=0.001); however, no concurrent relationship with cellular activation marker expression was found. In subjects with CHF, monocytes, TGF-β, IL-10, CD11b/CD18 and CXCR1 expression in peripheral blood may act as novel biomarkers of immune activation and remodelling. Given the importance of dyspnea and the relationship of pulmonary microvascular pressure to the NYHA classification, we suggest these findings may reflect a contribution by the lung.
authors.affiliation: Intensive and Critical Care Unit, Flinders Medical Centre, Adelaide, Australia. dani.dixon@flinders.edu.au
authors.forename: Dani-Louise
authors.initials: DL
authors.lastname: Dixon
authors.forename: Kim M
authors.initials: KM
authors.lastname: Griggs
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bersten
authors.forename: Carmine G
authors.initials: CG
authors.lastname: De Pasquale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000145:classification / Q000150:complications* / Q000453:epidemiology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D053208:Kaplan-Meier Estimate; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017493:Leukocyte Common Antigens