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 (CB3)
infection in mice, we found that
cadmium (Cd) accumulates in the kidney, whereas
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) accumulates in the liver. To study if CB3
infection affects the synthesis of the
Cd-binding protein metallothionein (MT) and the
TCDD-binding/detoxifying
cytochrome P-450 (CYP-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 alpha (IFN-alpha) and -beta (IFN-beta) were measured in CB3-infected mice and in mice treated with the
interferon-inducer
polyinosinic/polycytidylic acid (
poly I/C). Virus or
poly I/C was administered intraperitoneally (i.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 (P < 0.01 in infected mice and P < 0.001 in infected,
TCDD-treated mice).
TCDD alone induced a 10-fold increase in
CYP1A1 activity (P < 0.001), whereas
infection alone suppressed the normal
CYP1A1 activity by 75% (P < 0.001).
Infection also suppressed the
TCDD-induced
CYP1A1 activity by approximately 30% (n.s.).
Poly I/C suppressed
CYP1A1 by 20-25% (n.s.) at both basal and
TCDD-induced levels. Serum IFN-alpha and IFN-beta 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-alpha and IFN-beta 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.