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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Enhancement of coxsackievirus B4 virulence by indomethacin
Abstract:
The safety of nonsteroidal anti-inflammatory agents in viral infections was assessed in a mouse model of coxsackievirus B4 neonatal myocarditis. Two-day-old mice were infected intraperitoneally with 10(4) TCID50 coxsackievirus B4 and then randomized to receive indomethacin or saline for 7 days. A number of them were killed on designated days. Mortality, viral titers, antibody, and interferon levels plus histopathologic changes in the heart were compared. Among treated animals, mortality was greater (22/45 vs 7/27; p = 0.07) and viral titers were higher on days 4 and 7 (p = 0.038 and 0.028, respectively). Interferon levels were lower on days 4 and 7 (p = 0.028 and 0.008, respectively), and histopathologic changes were more extensive on days 7 and 21 (p = 0.008 and 0.028, respectively). These findings show that indomethacin decreased interferon production, increased coxsackievirus4 titers, and enhanced the virulence of coxsackievirus B4. These results raise significant concerns about the safety of indiscriminate use of nonsteroidal anti-inflammatory agents during severe viral infections.
Insights
Nonsteroidal anti-inflammatory drugs like indomethacin may worsen severe viral infections. This study found indomethacin increased mortality and coxsackievirus B4 virulence in neonatal mice, raising safety concerns.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Neonatal myocarditis is a severe condition often caused by viral infections.
- Nonsteroidal anti-inflammatory agents (NSAIDs) are commonly used for inflammation but their safety in viral infections is not fully understood.
Purpose of the Study:
- To assess the safety and impact of indomethacin, a NSAID, in a mouse model of coxsackievirus B4 neonatal myocarditis.
Main Methods:
- Two-day-old mice were infected with coxsackievirus B4 and treated with indomethacin or saline for seven days.
- Evaluated outcomes included mortality, viral titers, antibody and interferon levels, and cardiac histopathology.
Main Results:
- Indomethacin treatment led to increased mortality (p=0.07) and higher viral titers on days 4 and 7 (p=0.038, p=0.028).
- Interferon levels were significantly lower (p=0.028, p=0.008) and cardiac histopathologic changes were more extensive (p=0.008, p=0.028) in indomethacin-treated mice.
- Indomethacin decreased interferon production, elevated viral loads, and enhanced coxsackievirus B4 virulence.
Conclusions:
- Indomethacin administration negatively impacted the immune response and disease severity in coxsackievirus B4-induced neonatal myocarditis.
- These findings indicate potential risks associated with the non-selective use of NSAIDs during severe viral infections.
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