Immunomodulatory effect of pentoxifylline in suppressing experimental autoimmune myocarditis.
Although a recent clinical study reported the beneficial effects of pentoxifylline (PTX), a phosphodiesterase inhibitor, on both symptoms and cardiac function in dilated cardiomyopathy (DCM), the precise mechanism of the drug has not been delineated. This study examined the efficacy of PTX in the treatment of experimental autoimmune myocarditis (EAM), as a model of the autoimmune mechanism involved in DCM. Oral PTX, or saline as control, was administered to Lewis rats at 150mg/kg body weight per day bid daily from 5 days before immunization with cardiac myosin until death on Day 21. Histological examination of the hearts showed PTX significantly reduced the severity of EAM. mRNA expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-6, and IL-10 was significantly reduced in peripheral blood mononuclear cells, but expression of IL-4 and IL-6 was upregulated in heart tissue. PTX in vitro could suppress T cell proliferation and inhibit TNF-alpha and interferon-gamma production. In conclusion, the immunomodulatory effects of PTX had a significant therapeutic result in EAM. This is the first report to describe such an effect of PTX in a specific animal model for DCM.
Takehana
Hitoshi
H
Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. takehana@med.kitasato-u.ac.jp
Inomata
Takayuki
T
Niwano
Hiroe
H
Nishii
Mototsugu
M
Matsuda
Chieko
C
Kohno
Ken
K
Machida
Yoji
Y
Izumi
Tohru
T
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D066298:In Vitro Techniques; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D010431:Pentoxifylline / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D010431:Pentoxifylline