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Published on: July 17, 2012
Contractile depression and expression of proinflammatory cytokines and iNOS in viral myocarditis
G L Freeman1, J T Colston, M Zabalgoitia
1Division of Cardiology, University of Texas Health Science Center at San Antonio, USA.
Abstract:
We assessed two strains of mice [CD-1 and C3H.HeJ (C3H)] with different responses to coxsackievirus B3 (CVB3) infection at 7, 14, and 21 days after inoculation with 10(5) pfu of CVB3. CD-1 mice developed inflammatory lesions at 7 days that nearly recovered by 21 days; C3H mice demonstrated persistence of infiltrates. Although there were differences in the baseline fractional shortening, it was further reduced at 7 and 14 days in both strains. It recovered in CD-1 mice but remained depressed at 21 days in C3H mice. Interleukin-6 and tumor necrosis factor-alpha transcripts were increased in both strains at 7 days. Levels dropped to near control in CD-1 mice at 21 days but remained elevated in C3H mice. Interleukin-1 beta was minimally elevated in CD-1 mice but increased progressively in C3H mice. mRNA for the inducible form of NO synthase (iNOS) was increased at 7 days in the CD-1 mice, returning to baseline by 14 days; it rose progressively in C3H mice, with a fivefold increase at 21 days. We conclude that mice infected with CVB3 show increased expression of proinflammatory cytokines as well as iNOS associated with reduced contractile performance. In more susceptible mice, contractile depression and cytokine and iNOS expression are more pronounced.
Insights
Coxsackievirus B3 (CVB3) infection causes inflammation and reduced heart function in mice. More susceptible mice exhibit prolonged inflammation and cardiac dysfunction due to elevated cytokines and inducible nitric oxide synthase (iNOS).
Area of Science:
- Virology
- Immunology
- Cardiology
Background:
- Coxsackievirus B3 (CVB3) is a significant cause of viral myocarditis.
- Different mouse strains exhibit varying susceptibility to viral infections.
- Understanding host-pathogen interactions is crucial for developing therapeutic strategies.
Purpose of the Study:
- To compare the differential responses of CD-1 and C3H.HeJ (C3H) mice to CVB3 infection.
- To investigate the role of inflammatory markers and inducible nitric oxide synthase (iNOS) in CVB3-induced myocarditis.
- To correlate cardiac function with inflammatory responses in susceptible and resistant mouse models.
Main Methods:
- Two mouse strains (CD-1 and C3H) were inoculated with CVB3.
- Histopathological analysis of cardiac lesions was performed at 7, 14, and 21 days post-infection.
- Cardiac function was assessed by measuring fractional shortening.
- Gene expression analysis of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and iNOS was conducted.
Main Results:
- CD-1 mice showed transient inflammation and recovery, while C3H mice exhibited persistent inflammatory infiltrates.
- Fractional shortening was reduced in both strains at 7 and 14 days, with recovery in CD-1 mice but persistent depression in C3H mice.
- Pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and iNOS expression were significantly elevated in C3H mice compared to CD-1 mice, particularly at later time points.
Conclusions:
- CVB3 infection induces pro-inflammatory cytokine and iNOS expression, leading to reduced cardiac contractility in mice.
- Susceptibility to CVB3-induced myocarditis is strain-dependent, with C3H mice demonstrating a more severe and persistent inflammatory and cardiac response.
- Elevated iNOS and cytokine levels are associated with more pronounced and prolonged cardiac dysfunction in susceptible hosts.
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