Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on trace elements, inflammation and viral clearance in the myocardium during Coxsackievirus B3 infection in mice

myocarditic coxsackievirus B3 ŽCB3. infection in adult male A J mice was used to investigate the effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin ŽTCDD. exposure on mortality and on inflammatory lesion, virus and trace element contents of the heart. The mice were injected with four weekly intraperitoneal Ži.p.. injections of TCDD Ža loading dose of 5 g kg followed by three maintenance doses of 1.4 g kg.. To reach a steady-state body burden of TCDD the mice were allowed a 90-day recovery period before infection with CB3 virus. TCDD increased the infection-induced mortality rate, whereas in TCDD-exposed mice, heart lesions at day 7 after the virus inoculation Žmedian value 0.67% of the tissue section area; interquartile range 0.28; not statistically significant. were one-third of that in non-exposed infected mice Ž2.07% of the tissue section area; interquartile range 3.06.. The size of the inflammatory heart lesion correlated to the amount of virus Žrs 0.829, P 0.01. as well as to the calcium ŽCa: rs 0.725, P 0.01. and the magnesium ŽMg: rs 0.615, P 0.05. contents. In TCDD-exposed mice in situ hybridisation of viral RNA in the myocardium at day 7 showed a tendency to decreased amounts of virus, as well as a less pronounced increase in myocardial Ca content, both supporting a milder myocardial disease after TCDD exposure. No effect of TCDD exposure was seen on the zinc ŽZn. or selenium ŽSe. levels in the myocardium. In conclusion, although TCDD seemed to have a limiting effect on viral replication and the development of the inflammatory lesion in the myocardium, mortality was increased by TCDD in this infection model. However, TCDD had no significant effects on the selected trace elements that could be of importance for the severity of the inflammatory lesion ŽCa, Se., for the local host response activation ŽZn. or for the development of myocardial disease complications ŽMg.. Accordingly, the increased mortality may be a result of an infection-induced increase in TCDD toxicity to vital organs other than the heart, and or a TCDD-induced change in the tissue affinity and virulence of the virus, possibly causing involvement of other target organs in the infectious process and changed pathogenesis.