Effects of the antiviral WIN 54954 and the immune modulator LS 2616 on cachectin/TNF and gamma-interferon responses during viral heart disease.
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.
Toxicology and Safety Assessment, Kabi Pharmacia AB, Helsingborg, Sweden.
N G
NG
Ilbäck
L
L
Wesslén
K
K
Pauksen
T
T
Stålhandske
G
G
Friman
J
J
Fohlman
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000276:immunology; D029822:Enterovirus B, Human; D005260:Female; D006912:Hydroxyquinolines / Q000494:pharmacology; D007371:Interferon-gamma / Q000187:drug effects* / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D006912:Hydroxyquinolines; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; C062554:Win 54954; C045282:roquinimex; D007371:Interferon-gamma