Linked Life Data

7946395

Source:http://linkedlifedata.com/resource/pubmed/id/7946395

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1994-12-28
pubmed:abstractText
Chronic pulmonary hypertension is associated with significant vascular remodeling. We demonstrated recently in the monocrotaline (MCT) and chronic hypoxia rat models of pulmonary hypertension that treatment with platelet-activating factor (PAF) antagonists inhibited the development of chronic pulmonary hypertension. PAF and other lipid mediators interact with interleukin-1. We postulated that chronic treatment with a recombinant human interleukin-1 receptor antagonist (IL-1ra) would inhibit development of chronic pulmonary hypertension in animal models. Rats were either injected with (60 mg/kg) MCT or exposed to a stimulated high altitude of 16,000 feet; half of the animals were treated with twice-daily injections (2 mg/kg) of IL-1ra. At 3 wk after MCT injection or 3 wk of hypoxic exposure, pulmonary artery pressure and right heart ventricle weight/(left ventricle and septum weight), RV/(LV + S), were measured. IL-1ra treatment reduced pulmonary hypertension and right heart hypertrophy in the MCT model, but not in the chronic hypoxia model. Measurement of lung homogenate IL-1 alpha by radioimmunoassay showed elevated levels in the MCT-treated rats throughout the 3-wk observation period. IL-1ra treatment reduced the levels of IL-1 alpha in lung tissue in most of the MCT-treated rats. MCT treatment was also associated with an increase in lung mRNA for IL-1 alpha, IL-1 beta, and IL-1ra. Immunohistology, using an antibody against rat IL-1 alpha, revealed staining of alveolar structures and of vascular and bronchial smooth muscle. In situ hybridization using a human IL-1 alpha cDNA probe demonstrated increased expression of the IL-1 alpha gene in the lung cells after endotoxin or MCT treatment. Northern blot analysis demonstrated low-level expression of IL-1 alpha mRNA in extracts of normal rat lung and increased expression after endotoxin or MCT treatment. We conclude that chronic treatment with human IL-1ra inhibited the development of pulmonary hypertension in the inflammatory (MCT) model, but not in the chronically hypoxic rats. This result indicates that IL-1 participates in the pathogenesis of some forms of pulmonary hypertension.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
664-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7946395-Animals, pubmed-meshheading:7946395-Anoxia, pubmed-meshheading:7946395-Blood Pressure, pubmed-meshheading:7946395-Disease Models, Animal, pubmed-meshheading:7946395-Gene Expression Regulation, pubmed-meshheading:7946395-Humans, pubmed-meshheading:7946395-Hypertension, Pulmonary, pubmed-meshheading:7946395-Hypertrophy, Right Ventricular, pubmed-meshheading:7946395-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:7946395-Interleukin-1, pubmed-meshheading:7946395-Lung, pubmed-meshheading:7946395-Male, pubmed-meshheading:7946395-Monocrotaline, pubmed-meshheading:7946395-Pulmonary Artery, pubmed-meshheading:7946395-RNA, Messenger, pubmed-meshheading:7946395-Rats, pubmed-meshheading:7946395-Rats, Sprague-Dawley, pubmed-meshheading:7946395-Receptors, Interleukin, pubmed-meshheading:7946395-Recombinant Proteins, pubmed-meshheading:7946395-Sialoglycoproteins
pubmed:year
1994
pubmed:articleTitle
Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline.
pubmed:affiliation
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't