RGD Reference Report - Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline. - Rat Genome Database

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Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline.

Authors: Voelkel, NF  Tuder, RM  Bridges, J  Arend, WP 
Citation: Voelkel NF, etal., Am J Respir Cell Mol Biol. 1994 Dec;11(6):664-75.
RGD ID: 4143197
Pubmed: PMID:7946395   (View Abstract at PubMed)
DOI: DOI:10.1165/ajrcmb.11.6.7946395   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  IDA 4143197 RGD 
pulmonary hypertension  ISOIL1RN (Homo sapiens)4143197; 4143197 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Mus musculus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Homo sapiens)
IL1RN  (interleukin 1 receptor antagonist)


Additional Information