Immunoglobulin treatment ameliorates murine myocarditis associated with reduction of neurohumoral activity and improvement of extracellular matrix change.
OBJECTIVE
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.
Kishimoto
C
C
Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan. kkishi@kuhp.kyoto-u.ac.jp
Takamatsu
N
N
Kawamata
H
H
Shinohara
H
H
Ochiai
H
H
D000818:Animals; D018188:Cardiovirus Infections / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004686:Encephalomyocarditis virus; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000097:blood*; D005109:Extracellular Matrix / Q000473:pathology*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D009638:Norepinephrine / Q000097:blood*; D011897:Random Allocation
D016756:Immunoglobulins, Intravenous; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D009638:Norepinephrine; D004837:Epinephrine