Interleukin 1 bioactivity in the lungs of rats with monocrotaline-induced pulmonary hypertension.
A single subcutaneous injection of monocrotaline in rats provokes lung injury, inflammation, and progressive pulmonary hypertension. The specific mediators of the lung injury and inflammation and the relation of these events to the ensuing hypertensive pulmonary vascular disease are not understood. Since the monokine interleukin 1 (IL-1) has been implicated in acute inflammatory reactions, the present study tested the hypotheses that monocrotaline promotes the appearance of IL-1 in the bronchoalveolar spaces of treated rats and that accumulation of the monokine coincides temporally with development of lung injury, inflammation, and/or pulmonary hypertension. As expected, monocrotaline administration was associated with an early phase of pulmonary edema, manifest at Day 7 post-treatment as an increase in the lung wet-to-dry weight ratio, followed at Day 14 post-treatment by development of pulmonary hypertension as evidenced by progressive right ventricular hypertrophy. Lung inflammation also was present at Days 14 and 21 after monocrotaline as indicated by the accumulation of leukocytes in the bronchoalveolar lavage fluid and by an increase in the lung tissue activity of the granulocyte-specific enzyme myeloperoxidase. Interleukin 1, bioassayed in bronchoalveolar lavage fluid using the standard D10 T-cell assay system, was increased slightly at Day 4 postmonocrotaline, returned to baseline at Day 7, and was markedly elevated at Days 14 and 21 after monocrotaline treatment. These observations indicate that increases in the bronchoalveolar lavage fluid content of IL-1 bioactivity are temporally related to the evolution of monocrotaline-induced lung injury, inflammation, and pulmonary hypertension and suggest that the monokine may play a pathogenetic role in these events.
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains
D007375:Interleukin-1; D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline