1. Colchicine aggravates coxsackievirus B3 infection in mice.
- Author
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Smilde BJ, Woudstra L, Fong Hing G, Wouters D, Zeerleder S, Murk JL, van Ham M, Heymans S, Juffermans LJ, van Rossum AC, Niessen HW, Krijnen PA, and Emmens RW
- Subjects
- Animals, Colchicine adverse effects, Colchicine pharmacology, Coxsackievirus Infections mortality, Disease Models, Animal, Enterovirus B, Human physiology, Heart drug effects, Heart virology, Humans, Male, Mice, Mice, Inbred C3H, Myocarditis drug therapy, Myocarditis mortality, Pancreas drug effects, Pancreas virology, Spleen drug effects, Spleen virology, Treatment Outcome, Viral Load drug effects, Colchicine administration & dosage, Coxsackievirus Infections drug therapy, Myocarditis virology, Pancreas pathology, Spleen pathology
- 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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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