title: The effect of beta-blockers on the adaptive immune system in chronic heart failure.
abstract: It remains possible that the benefit from beta-blockers (BBs) in chronic heart failure (CHF) may not entirely be derived from a class-specific effect. Several experimental reports have alluded to the capability of immunomodulation by individual BBs. Given the increasingly recognized importance of the immune system in the pathogenesis of CHF, we studied the effects of BBs on the circulating immune system of these patients. Blood samples from CHF outpatients were prospectively analyzed using flow cytometry and gating software. Results were analyzed against comprehensive clinical details that were recorded during sample donation, including the type of BB administered. 273 blood samples were analyzed from 141 CHF patients, with an average ejection fraction of 31.9% and a mean age of 69.1 years. Patients taking carvedilol had a significantly lower expression of CD107a on cytotoxic T cells compared to bisoprolol (P= 0.001) and nebivolol (P= 0.008). They also had a significantly lower expression of HLA-DR on lymphocytes (P < 0.001 and P= 0.009 for bisoprolol and nebivolol, respectively). Cytotoxic T cells and lymphocytes expressing HLA-DR have been implicated in the pathogenesis of CHF. The fact that carvedilol, but not other commonly used beta-blockers, appears to modulate these important parameters, supports the concept that important differences exist between these agents, which may affect outcomes in CHF.
authors.affiliation: North West Regional Heart Centre and Transplant Unit, University of South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester M23 9LT, UK. doctorshaw@doctors.org.uk
authors.forename: Steven M
authors.initials: SM
authors.lastname: Shaw
authors.forename: Teresa
authors.initials: T
authors.lastname: Coppinger
authors.forename: Carolyn
authors.initials: C
authors.lastname: Waywell
authors.forename: Louise
authors.initials: L
authors.lastname: Dunne
authors.forename: Louise D
authors.initials: LD
authors.lastname: Archer
authors.forename: William R
authors.initials: WR
authors.lastname: Critchley
authors.forename: Nizar
authors.initials: N
authors.lastname: Yonan
authors.forename: James E
authors.initials: JE
authors.lastname: Fildes
authors.forename: Simon G
authors.initials: SG
authors.lastname: Williams
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000368:Aged; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use; D017298:Bisoprolol / Q000494:pharmacology / Q000627:therapeutic use; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D002908:Chronic Disease; D015331:Cohort Studies; D004492:Edetic Acid; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D002227:Carbazoles; D004983:Ethanolamines; D006684:HLA-DR Antigens; D011412:Propanolamines; D000068577:Nebivolol; D000077261:Carvedilol; D004492:Edetic Acid; D017298:Bisoprolol