Effects of coxsackievirus B3 infection on the acute-phase protein metallothionein and on cytochrome P-4501A1 involved in the detoxification processes of TCDD in the mouse

During acute infections, the synthesis of acute-phase proteins and other proteins participating in the host defence are stimulated in the liver and kidney. In previous studies of coxsackievirus B3 ŽCB3. infection in mice, we found that cadmium ŽCd. accumulates in the kidney, whereas 2,3,7,8-tetrachlorodibenzo-p-dioxin ŽTCDD. accumulates in the liver. To study if CB3 infection affects the synthesis of the Cd-binding protein metallothionein ŽMT. and the TCDD-binding detoxifying cytochrome P-450 ŽCYP-450. isozyme CYP1A1, the basal and TCDD-induced levels of serum MT and liver CYP1A1 isozyme were determined in healthy and CB3-infected A J mice. Furthermore, because interferons affect CYP450 activity, the serum levels of the interferons ŽIFN- . and - ŽIFN- . were measured in CB3-infected mice and in mice treated with the interferon-inducer polyinosinic polycytidylic acid Žpoly I C.. Virus or poly I C was administered intraperitoneally Ži.p.. on day 0 and 500 ng TCDD kg bodyweight on day 1. On day 4, CB3 infection had induced MT approximately 10-fold, regardless of TCDD treatment ŽP 0.01 in infected mice and P 0.001 in infected, TCDD-treated mice.. TCDD alone induced a 10-fold increase in CYP1A1 activity ŽP 0.001., whereas infection alone suppressed the normal CYP1A1 activity by 75% ŽP 0.001.. Infection also suppressed the TCDD-induced CYP1A1 activity by approximately 30% Žn.s... Poly I C suppressed CYP1A1 by 20 25% Žn.s.. at both basal and TCDD-induced levels. Serum IFN- and IFN- levels were undetectable in controls,in TCDD-treated and in the poly I C-treated groups on day 4, probably because the short IFN peak is detectable only hours after injection. Conversely, on day 4 of the infection, IFN- and IFN- were consistently raised in the TCDD-treated infected mice, whereas increased IFNs as a result of infection alone could be detected in only one individual. These results suggest that the normal host responses during acute infections down-regulate detoxifying processes in favour of acute-phase protein synthesis. This may explain the observed changed pattern of accumulation, excretion and toxicity of the environmental pollutants cadmium and TCDD during this common virus infection.