Enhancement of coxsackievirus B4 virulence by indomethacin

R Khatib1, M P Reyes, F Smith

  • 1Department of Medicine, Grace Hospital, Detroit, MI 48235.

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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