Colchicine aggravates coxsackievirus B3 infection in mice. (1st August 2016)

• Record Type: Journal Article
• Authors: Smilde, Bernard J.; Woudstra, Linde; Fong Hing, Gene; Wouters, Diana; Zeerleder, Sacha; Murk, Jean-Luc; van Ham, Marieke; Heymans, Stephane; Juffermans, Lynda J.M.; van Rossum, Albert C.; Niessen, Hans W.M.; Krijnen, Paul A.J.; Emmens, Reindert W.
• Is Part Of: International journal of cardiology. Volume 216(2016)
• Page Start: 58
• Page End: 65
• Publication Date: 2016-08-01
• Subjects: Colchicine -- Myocarditis -- Coxsackievirus B3 -- Mouse; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2016.04.144
• Languages: English
• ISSNs: 0167-5273

Abstract

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 (2 mg/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. Highlights: Myocarditis is commonly caused by viral infection and therefore difficult to treat. We investigated colchicine treatment in mice with coxsackievirus-induced myocarditis. Colchicine caused severe illness and destruction of the pancreas in infected mice. Colchicine aggravated coxsackievirus infection in both the heart and the pancreas. Colchicine may therefore not be suitable to treat patients with viral myocarditis.