title: Dexamethasone attenuates development of monocrotaline-induced pulmonary arterial hypertension.
abstract: Immunity and inflammation are well established factors in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether dexamethasone (Dex), a potent immunosuppressant, could prevent the development of monocrotaline (MCT)-induced PAH in rats as compared with pyrrolidine dithiocarbamate (PDTC) and its effect on the immune mechanism. PAH in rats (n = 66) was induced by MCT (50 mg/kg) injected intraperitoneally. Two days after MCT treatment, Dex (1.0 mg/kg) and PDTC (100 mg/kg) were administered once daily for 21 days. Samples were collected at 7, 14, and 21 days. Dex effectively inhibited MCT-induced PAH and reduced the T-helper (Th) 1 dominant cytokine response (interferon-γ) but up-regulated the Th2 one (interleukin 4). It increased the number of CD4+ T cells and decreased the number of CD8+ T cells around pulmonary arteries, upregulated the mRNA expression of fractalkine and downregulated that of CX3CR1 in the lung. Serum levels of interferon γ and interleukin 4 did not significantly differ from that of controls. Dex attenuated the process of MCT-induced PAH through its immunomodulatory property. Dex could be an appropriate therapy for PAH, although more studies are needed to define the appropriate treatment regimen.
authors: Department of Pediatrics, Shandong Provincial Hospital, Shandong University, 44 Wenxi Road, Ji'nan, 250012 Shandong Province, China.
authors: Wei
authors: W
authors: Wang
authors: Yu-Lin
authors: YL
authors: Wang
authors: Xiao-Ying
authors: XY
authors: Chen
authors: Yu-Tang
authors: YT
authors: Li
authors: Wei
authors: W
authors: Hao
authors: You-Peng
authors: YP
authors: Jin
authors: Bo
authors: B
authors: Han
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D065627:Familial Primary Pulmonary Hypertension; D005938:Glucocorticoids / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000473:pathology / Q000502:physiology; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; D005938:Glucocorticoids; D019707:Receptors, Chemokine; D015847:Interleukin-4; D016686:Monocrotaline; D003907:Dexamethasone; D007371:Interferon-gamma