title: β2-Agonist clenbuterol hinders human monocyte differentiation into dendritic cells.
abstract: Clenbuterol (CLB) is a beta2-adrenergic agonist commonly used in asthma therapy, but is also a non-steroidal anabolic drug often abused in sport doping practices. Here we evaluated the in vitro impact of CLB on the physiology and function of human monocytes and dendritic cells (DCs), instrumental in the development of immune responses. We demonstrate that CLB inhibits the differentiation of monocytes into DCs and this effect is specific and dependent on β2-adrenergic receptor (AR) activation. We found that CLB treatment reduced the percentage of CD1a(+) immature DCs, while increasing the frequency of monocytes retaining CD14 surface expression. Moreover, CLB inhibited tumor necrosis factor-alpha (TNF-alpha) enhanced IL-(interleukin)-10 and IL-6 production. In contrast, CLB did not modulate the phenotypic and functional properties of monocytes and DCs, such as the surface expression of HLA-DR, CD83, CD80 and CD86 molecules, cytokine production, immunostimulatory activity and phagocytic activity. Moreover, we found that CLB did not modulate the activation of NF-kB in DCs. Moreover, we found that the differentiation of monocytes into DCs was associated with a significant decrease of β2-ARs mRNA expression. These results provide new insights on the effect of CLB on monocyte differentiation into DCs. Considering the frequent illegal use of CLB in doping, our work suggests that this drug is potentially harmful to immune responses decreasing the supply of DCs, thus subverting immune surveillance.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: luciana.giordani@iss.it.
authors.forename: Luciana
authors.initials: L
authors.lastname: Giordani
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Noemi
authors.initials: N
authors.lastname: Cuzziol
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Del Pinto
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Maccari
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Massimi
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Pietraforte
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Viora
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D002976:Clenbuterol / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D002976:Clenbuterol
keywords: Clenbuterol; Doping drugs; Monocytes Dendritic cells; β(2)-adrenoceptor agonist