title: Colchicine aggravates coxsackievirus B3 infection in mice.
abstract: BACKGROUND
  There is a clinical need for immunosuppressive therapy that can treat myocarditis patients in the presence of an active viral infection. In this study we therefore investigated the effects of colchicine, an immunosuppressive drug which has been used successfully as treatment for pericarditis patients, in a mouse model of coxsackievirus B3(CVB3)-induced myocarditis.
  
  
  METHODS
  Four groups of C3H mice were included: control mice (n=8), mice infected with CVB3 (1×10(5) PFU, n=10), mice with colchicine administration (2mg/kg i.p, n=5) and mice with combined CVB3 infection and colchicine administration (n=10). After three days, the heart, pancreas and spleen were harvested and evaluated using (immuno)histochemical analysis and CVB3 qPCR.
  
  
  RESULTS
  Mice were terminated at day 3 post-virus infection as colchicine treatment rapidly resulted in severe illness and mortality in CVB3-infected mice. Colchicine significantly decreased the number of macrophages in the heart in CVB3-infected mice (p<0.01) but significantly increased the number of neutrophils (p<0.01). In the pancreas, colchicine caused complete destruction of the acini in the CVB3-infected mice and also significantly decreased macrophage (p<0.01) and increased neutrophil numbers (p<0.01). In the spleen, colchicine treatment of CVB3-infected mice induced massive apoptosis in the white pulp and significantly inhibited the virus-induced increase of megakaryocytes in the spleen (p<0.001). Finally, we observed that colchicine significantly increased CVB3 levels in both the pancreas and the heart.
  
  
  CONCLUSIONS
  Colchicine treatment in CVB3-induced myocarditis has a detrimental effect as it causes complete destruction of the exocrine pancreas and enhances viral load in both heart and pancreas.
authors.affiliation: Department of Pathology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Smilde
authors.affiliation: Department of Pathology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Institute for Cardiovascular Research of the Vrije Universiteit (ICaR-VU), VU University Medical Center, De Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Linde
authors.initials: L
authors.lastname: Woudstra
authors.affiliation: Department of Pathology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Gene
authors.initials: G
authors.lastname: Fong Hing
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Postbox 9892, 1006, AN, Amsterdam, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Postbox 9892, 1006, AN, Amsterdam, The Netherlands; Department of Hematology, Academic Medical Center, Postbox 22660, 1100, DD, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.affiliation: Department of Virology, University Medical Center Utrecht, Postbox 85500, 3508, GA, Utrecht, The Netherlands.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Murk
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Postbox 9892, 1006, AN, Amsterdam, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: van Ham
authors.affiliation: Department of Cardiology, Maastricht University Medical Center, Postbox 5800, 6202, AZ, Maastricht, The Netherlands.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
authors.affiliation: Department of Cardiology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Institute for Cardiovascular Research of the Vrije Universiteit (ICaR-VU), VU University Medical Center, De Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Lynda J M
authors.initials: LJ
authors.lastname: Juffermans
authors.affiliation: Department of Cardiology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Institute for Cardiovascular Research of the Vrije Universiteit (ICaR-VU), VU University Medical Center, De Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: Department of Pathology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Institute for Cardiovascular Research of the Vrije Universiteit (ICaR-VU), VU University Medical Center, De Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Pathology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Institute for Cardiovascular Research of the Vrije Universiteit (ICaR-VU), VU University Medical Center, De Postbox 7057, 1007, MB, Amsterdam, The Netherlands.
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
authors.affiliation: Department of Pathology, VU University Medical Center, Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Institute for Cardiovascular Research of the Vrije Universiteit (ICaR-VU), VU University Medical Center, De Postbox 7057, 1007, MB, Amsterdam, The Netherlands; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Postbox 9892, 1006, AN, Amsterdam, The Netherlands. Electronic address: r.emmens@vumc.nl.
authors.forename: Reindert W
authors.initials: RW
authors.lastname: Emmens
mesh_terms: D000818:Animals; D003078:Colchicine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000188:drug therapy / Q000401:mortality / Q000821:virology*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D013154:Spleen / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D003078:Colchicine
keywords: Colchicine; Coxsackievirus B3; Mouse; Myocarditis