Growth hormone interferes with the progression of myocarditis in rats.
In this study, we investigated whether recombinant human growth hormone (rhGH) influences the progression of myocarditis. We induced experimental autoimmune myocarditis in F344 rats by subcutaneous injection of cardiac myosin, and divided the rats into three groups: (1) control group, saline injection; (2) pre-treated group, subcutaneous injection of rhGH (100 mIU/rat/day for 10 days) before induction of experimental autoimmune myocarditis; and (3) post-treated group, subcutaneous injection of rhGH (100 mIU/rat/day for 10 days) after induction of experimental autoimmune myocarditis. On the 35th day after induction of experimental autoimmune myocarditis, all rats were sacrificed and the hearts were examined. The increase in body weight was smaller in the control group than the pre-treated group and the rate of heart weight/body weight was larger in the control group than in the two treated groups. Histopathologically, rats in the control group showed multifocal infiltration by inflammatory cells, mainly neutrophils, lymphocytes and macrophages, extensive fibrosis, and a higher proportion of mast cells in the inflamed region. In contrast, rats in the two treated groups showed only minor changes. We found that rhGH did not influence the distribution of lymphocytes in peripheral blood in the three groups, and that rhGH induced G1 checkpoint dysfunction, thereby arresting the cell cycle in G1 and inhibiting the proliferation of mast cells in vitro. These findings suggest a possible role for mast cells in the progression of myocarditis and the rhGH may be a candidate for use as a new tool to treat myocarditis.
Division of Basic Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. zong3961@kanazawa-med.ac.jp
Z P
ZP
Zong
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Matsui
A L
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Li
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Yamaguchi
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Katsuda
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Hayase
M L
ML
Fu
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D009205:Myocarditis / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms
D015704:CD4 Antigens; D016827:CD8 Antigens; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D017493:Leukocyte Common Antigens