Immunomodulation of experimental autoimmune myocarditis by pentoxifylline

Abstract

We designed the present study to provide evidence of the immunomodulatory effects of pentoxifylline (PTX) in experimental autoimmune myocarditis (EAM) in rats. PTX is xantine-derived agent known to inhibit the production of TNF-α and his beneficial effects have been reported in patients with dilated cardiomyopathy. In this study we examined the efficacy of PTX in the treatment of experimental autoimmune myocarditis as a paradigm of the autoimmune mechanisms involved in pathogenesis of dilated cardiomiopathy. Male DA rats immunized with porcine cardiac myosin were treated i.m. with PTX (200 mg/kg/day) over 7 days, begenning either on the day of immunization (early treatment group), or on day 14. postimmunization (late treatment group). Disease course and severity were evaluated by macroscopic score of the heart, heart weight/body weight ratio (Hw/Bw), histological and immunohistochemical analysis of cardiac tisssue. We found in our study that PTX exhibited both preventive and therapeutical effects in EAM.

U radu je ispitivan uticaj pentoksifilina (PTX) na razvoj i tok eksperimentalnog autoimunog miokarditisa pacova. Pentoksifilin je derivat ksantina sa inhibitornim efektom na produkciju TNF-α, a klinički je potvrđen i njegov pozitivan učinak u terapiji pacijenata sa dilatacionom kardiomiopatijom. U ispitivanju je testiran imunomodulatorni efekat PTX u tretmanu eksperimentalnog autoimunog miokarditisa koji predstavlja eksperimentalni model za proučavanje autoimunskih mehanizama uključenih u razvoj dilatacione kardiomiopatije. Pacovi DA soja imunizovani srčanim miozinom tretirani su pentoksifilinom u dozi od 200 mg/kg t.m., počev od 0.-6. dana (rani tretman), ili od 14.-20. dana (kasni tretman) u odnosu na termin imunizacije miozinom. Razvoj i intenzitet miokarditisa praćeni su analizom makroskopskih karakteristika srca, indeksa masa srca/telesna masa (Hwt/Bwt), histoloških i imunohistohemijskih analiza miokarda. Dobijeni rezultati su pokazali da PTX ispoljava profilaktičan i terapijski učinak u eksperimentalnom autoimunom miokarditisu.