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.
A myocarditic coxsackievirus B3 (CB3) infection in adult male A/J mice was used to investigate the effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure on mortality and on inflammatory lesion, virus and trace element contents of the heart. The mice were injected with four weekly intraperitoneal (i.p.) injections of TCDD (a loading dose of 5 microg/kg followed by three maintenance doses of 1.4 microg/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 (median 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 (2.07% of the tissue section area; interquartile range 3.06). The size of the inflammatory heart lesion correlated to the amount of virus (r(s) = 0.829, P < 0.01) as well as to the calcium (Ca: r(s) = 0.725, P < 0.01) and the magnesium (Mg: r(s) = -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 (Zn) or selenium (Se) 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 (Ca, Se), for the local host response activation (Zn) or for the development of myocardial disease complications (Mg). 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.
Funseth
Eva
E
Department of Medical Sciences, Uppsala University Hospital, Sweden.
Wesslén
Lars
L
Lindh
Ulf
U
Friman
Göran
G
Ilbäck
Nils-Gunnar
NG
D000818:Animals; D002118:Calcium / Q000737:chemistry; D003384:Coxsackievirus Infections / Q000150:complications* / Q000276:immunology; D004785:Environmental Pollutants / Q000009:adverse effects*; D007249:Inflammation; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D012367:RNA, Viral; D012643:Selenium / Q000737:chemistry; D013723:Teratogens / Q000633:toxicity*; D014131:Trace Elements / Q000032:analysis*; D014779:Virus Replication; D015032:Zinc / Q000032:analysis
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012367:RNA, Viral; D013723:Teratogens; D014131:Trace Elements; D012643:Selenium; D015032:Zinc; D002118:Calcium