title: Modulation of human monocyte/macrophage activity by tocilizumab, abatacept and etanercept: An in vitro study.
abstract: Tocilizumab, etanercept and abatacept are biological drugs used in the therapy of Rheumatoid Arthritis (RA). Their mechanism of action is well documented but their direct effects on human monocytes/macrophages have not been fully investigated. The objective of this study was to evaluate in vitro the influence of these drugs on monocytes/macrophages from healthy volunteers. Human monocytes were isolated from healthy anonymous volunteers and cultured as such or differentiated to monocyte-derived macrophages (MDMs). The effect of tocilizumab, etanercept and abatacept (at concentrations similar to those in plasma of patients) on superoxide anion production, matrix metalloproteinase-9 (MMP-9) gene expression and activity, Peroxisome Proliferator-Activated Receptor (PPAR)γ expression and cell phenotype was evaluated. Exposure of monocytes/macrophages to tocilizumab, etanercept or abatacept resulted in a significant decrease of the PMA-induced superoxide anion production. Interestingly, the expression of PPARγ was significantly increased only by tocilizumab, while etanercept was the only one able to significantly reduce MMP-9 gene expression and inhibit the LPS-induced MMP-9 activity in monocytes. When etanercept and abatacept were added to the differentiating medium, both significantly reduced the amount of CD206(+)MDM. This study demonstrates that etanercept, abatacept and tocilizumab affect differently human monocytes/macrophages. In particular, the IL-6 antagonist tocilizumab seems to be more effective in inducing an anti-inflammatory phenotype of monocytes/macrophages compared to etanercept and abatacept, also in light of the up-regulation of PPARγ whose anti-inflammatory effects are well recognised.
authors.affiliation: Department of Health Sciences, School of Medicine, University of Piemonte Orientale, Via Solaroli, 17, 28100 Novara, Italy.
authors.forename: Joyce Afrakoma
authors.initials: JA
authors.lastname: Obeng
authors.affiliation: Department of Health Sciences, School of Medicine, University of Piemonte Orientale, Via Solaroli, 17, 28100 Novara, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoruso
authors.affiliation: Azienda Ospedaliera-Universitaria Maggiore della Carità, Novara, Italy.
authors.forename: Gian Luca Ermanno
authors.initials: GL
authors.lastname: Camaschella
authors.affiliation: Azienda Ospedaliera-Universitaria Maggiore della Carità, Novara, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sola
authors.affiliation: Department of Health Sciences, School of Medicine, University of Piemonte Orientale, Via Solaroli, 17, 28100 Novara, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brunelleschi
authors.affiliation: Department of Health Sciences, School of Medicine, University of Piemonte Orientale, Via Solaroli, 17, 28100 Novara, Italy. Electronic address: fresu@med.uniupo.it.
authors.forename: Luigia Grazia
authors.initials: LG
authors.lastname: Fresu
mesh_terms: D000069594:Abatacept / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000068800:Etanercept / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D047495:PPAR gamma; D000069594:Abatacept; D020780:Matrix Metalloproteinase 9; C502936:tocilizumab; D000068800:Etanercept
keywords: Biological drugs; Inflammation; Monocytes/macrophages