The effects of the anti picornaviral
drug WIN 54954 (5-(5-(2.6-dichloro-4-(4.5-dihydro-2-oxazolyl)phenoxy)pentyl)-3-me thyl- isoxazole) and the immune modulator
LS 2616 (Quinoline-3-carboxamide) on plasma
cachectin/TNFa and g-
interferon (IFN-g) responses were investigated during the
clinical course of a myocarditic coxsackievirus B3 (CB3)
infection in the mouse. Virus as well as inflammatory and necrotic lesions were found in the hearts on days 4 and 7 post inoculation (p.i.), respectively. This was demonstrated using in situ virus RNA hybridization and immune histological techniques with
monoclonal antibodies against lymphocyte subsets. The CB3
infection increased TNFa levels during the first three days of disease. This response was suppressed by
WIN 54954 and
LS 2616. IFN-g was decreased in infected mice in the late phase of the disease (day 11).
Therapy, however, was protective, and
WIN 54954 even tended to increase the IFN-g response at day 5, corresponding to the time when
viremia peaks. These results indicate that
cytokines may serve as prognostic markers in the
therapy of
infectious diseases and also that
WIN 54954 and
LS 2616 are both possible candidates for treatment of
coxsackievirus infections in man. It is suggested that a combined
antiviral and immune stimulatory treatment could be of future value.