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EXPERIMENTAL STUDY

Immunoglobulin treatment ameliorates murine myocarditis associated with reduction of neurohumoral activity and improvement of extracellular matrix change

Chiharu Kishimoto, MD, PhD^*, Nami Takamatsu, RN^*, Hiroshi Kawamata, MD, Hiromichi Shinohara, MD, PhD and Hiroshi Ochiai, MD, PhD

^* Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Department of Oriental Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Department of Human Science, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

Manuscript received December 28, 1999; revised manuscript received June 15, 2000, accepted July 25, 2000.

Reprint requests and correspondence: Dr. Chiharu Kishimoto, The Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
kkishi{at}kuhp.kyoto-u.ac.jp

OBJECTIVES

We examined effects of immunoglobulin on murine myocarditis induced by encephalomyocarditis virus, not pathogenic to humans, and analyzed the plasma cytokine and catecholamine levels and the changes of the extracellular matrix with or without the treatment.

BACKGROUND

We have previously shown that immunoglobulin therapy suppressed murine coxsackievirus B3 myocarditis by an antiviral effect. However, it is not yet determined whether beneficial effects of immunoglobulin for myocarditis are due to antiviral effects or to other unknown effects.

METHODS

Antiviral activity of human immunoglobulin (Polyglobin-N) against encephalomyocarditis virus was determined in vitro. Immunoglobulin (1 g/kg/day) was administered intraperitoneally to the virus-infected mice daily for two weeks, beginning simultaneously with virus inoculation in experiment I and on day 14 after virus inoculation in experiment II.

RESULTS

Antiviral activity of immunoglobulin could not be detected in the assay of a plaque-reduction method in vitro. The in vivo study showed that immunoglobulin administration ameliorated both myocardial necrosis with interstitial fibrin deposition in experiment I and interstitial fibrosis with the improvement of ventricular remodeling in experiment II by the reduction of plasma catecholamines, interferon-alpha, and soluble intercellular adhesion molecule-1.

CONCLUSIONS

Immunoglobulin therapy could suppress myocarditis associated with the improvement of extracellular matrix changes by the reduction of neurohumoral activity.

Abbreviations and Acronyms   EMC virus = encephalomyocarditis virus   E = epinephrine   IFN- = interferon-   NE = norepinephrine   PFU = plaque-forming units   sICAM-1 = soluble intercellular adhesion molecule-1   VERO cells = African green monkey kidney cells

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