Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 18, 2016; 8(17): 726-730
Published online Jun 18, 2016. doi: 10.4254/wjh.v8.i17.726
Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats
Karen Louise Thomsen, Holger Jon Møller, Jonas Heilskov Graversen, Nils E Magnusson, Søren K Moestrup, Hendrik Vilstrup, Henning Grønbæk
Karen Louise Thomsen, Hendrik Vilstrup, Henning Grønbæk, Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
Holger Jon Møller, Department of Clinical Biochemistry, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
Jonas Heilskov Graversen, Affinicon Aps, Incuba Science Park, DK 8200 Aarhus N, Denmark
Jonas Heilskov Graversen, Søren K Moestrup, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense C, Denmark
Nils E Magnusson, Department of Clinical Medicine, Faculty of Health, Medical Research Laboratory, Aarhus University, DK-8000 Aarhus C, Denmark
Søren K Moestrup, Department of Biomedicine, University of Aarhus, DK-8000 Aarhus C, Denmark
Author contributions: Thomsen KL, Møller HJ and Grønbæk H conceived and designed the study; Thomsen KL and Magnusson NE acquired the data and analysed the samples; Thomsen KL, Vilstrup H and Grønbæk H analysed and interpreted the data; Thomsen KL drafted the manuscript; Møller HJ, Graversen JH, Moestrup SK, Vilstrup H and Grønbæk H critically revised the manuscript for important intellectual content; all authors saw and approved the final manuscript.
Supported by The NOVO Nordisk foundation; the Aarhus University Research Foundation; and Clinical Institute, Aarhus University, Denmark.
Institutional animal care and use committee statement: The study was performed in accordance with local and national guidelines for animal welfare and reviewed and approved by the national Animal Ethics Committee, protocol No. 2010/561-1918.
Conflict-of-interest statement: Møller HJ, Graversen JH and Moestrup SK are inventors for the CD163-dexamethasone conjugate and minority shareholders in Affinicon Aps. All other authors have nothing to disclose.
Data sharing statement: Dataset is available from the corresponding author at karethom@rm.dk.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Karen Louise Thomsen, MD, PhD, Department of Hepatology and Gastroenterology, Aarhus University Hospital, 44 Nørrebrogade, DK-8000 Aarhus C, Denmark. karethom@rm.dk
Telephone: +45-78-463897 Fax: +45-78-462740
Received: February 22, 2016
Peer-review started: February 22, 2016
First decision: March 24, 2016
Revised: May 4, 2016
Accepted: May 31, 2016
Article in press: June 2, 2016
Published online: June 18, 2016
Processing time: 113 Days and 9.6 Hours
Core Tip

Core tip: We aimed to study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. The central finding of the study was a reduction in liver mRNA and plasma levels of the acute phase protein α-2-macroglobulin, and plasma tumour necrosis factor-α and interleukin 6 by administration of the conjugate prior to a lipopolysaccharide-induced inflammatory response. This anti-acute phase effect exceeded that of the therapeutic dexamethasone dose and did not cause systemic adverse effects. Thus, the antibody conjugate may be a potential candidate in future anti-inflammatory macrophage-directed therapy, e.g., in liver diseases with Kupffer cells activation.