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Effects of levamisole, an immunomodulator, upon murine encephalomyocarditis virus myocarditis
C Kishimoto1, H Takada, Y Hiraoka
1Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Abstract:
To test the therapeutic efficacy of levamisole, 5-week-old DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units of encephalo-myocarditis virus. Levamisole (2.5 mg/kg/per day) was administered intraperitoneally daily, starting simultaneously with the virus inoculation, in experiment I for 14 days, and daily on days 14 to 28 in experiment II in mice that survived to 14 days after virus inoculation. In experiment I, survival was higher, the severity of myocarditis was less, and myocardial virus titers were lower in treated than in untreated animals. In experiment II, levamisole was not effective. No significant changes in serum neutralizing antibody titers occurred in either experiment. Furthermore, levamisole prevented associated lymphoid organ atrophy induced by the virus infection. An additional in vitro study revealed the absence of anti-viral activity of the drug. Thus, levamisole may have favorable effects upon encephalomyocarditis virus myocarditis by preventing the virus-induced lymphoid organ atrophy and reducing myocardial virus replication in the acute stage.
Insights
Levamisole treatment improved survival and reduced myocarditis severity in encephalomyocarditis virus-infected mice during the acute phase. The drug also prevented lymphoid organ atrophy, suggesting a protective role.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Encephalomyocarditis virus (EMCV) causes myocarditis, a significant cardiac inflammation.
- Viral infections can lead to lymphoid organ atrophy, impacting immune function.
- Levamisole is an immunomodulatory drug with potential therapeutic applications.
Purpose of the Study:
- To evaluate the therapeutic efficacy of levamisole in a mouse model of EMCV-induced myocarditis.
- To investigate levamisole's effects on viral load, myocarditis severity, survival rates, and lymphoid organ integrity.
- To determine if levamisole possesses direct antiviral activity in vitro.
Main Methods:
- DBA/2 mice were inoculated with EMCV and treated with levamisole daily.
- Experiment I involved simultaneous administration of levamisole and virus for 14 days.
- Experiment II administered levamisole to surviving mice from day 14 to 28 post-infection; in vitro antiviral assays were also performed.
Main Results:
- Levamisole treatment in Experiment I significantly increased survival, reduced myocarditis severity, and lowered myocardial viral titers.
- The drug effectively prevented virus-induced lymphoid organ atrophy.
- Levamisole showed no efficacy in Experiment II and no direct antiviral activity in vitro.
Conclusions:
- Levamisole demonstrates therapeutic potential against EMCV myocarditis, particularly in the acute stage.
- The beneficial effects appear linked to preventing lymphoid organ atrophy and reducing viral replication.
- Levamisole's immunomodulatory properties, rather than direct antiviral action, likely mediate its protective effects.