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: Bernard J Smilde, Linde Woudstra, Gene Fong Hing, Diana Wouters, Sacha Zeerleder, Jean-Luc Murk, Marieke van Ham, Stephane Heymans, Lynda J M Juffermans, Albert C van Rossum, Hans W M Niessen, Paul A J Krijnen, Reindert W Emmens
• Journal: International journal of cardiology (Int J Cardiol) Vol. 216 Pg. 58-65 (Aug 01 2016) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 27140338 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Colchicine

Topics

• Animals
• Colchicine (administration & dosage, adverse effects, pharmacology)
• Coxsackievirus Infections (drug therapy, mortality)
• Disease Models, Animal
• Enterovirus B, Human (physiology)
• Heart (drug effects, virology)
• Humans
• Male
• Mice
• Mice, Inbred C3H
• Myocarditis (drug therapy, mortality, virology)
• Pancreas (drug effects, pathology, virology)
• Spleen (drug effects, pathology, virology)
• Treatment Outcome
• Viral Load (drug effects)