Relationship between interleukin-1 beta and platelet-activating factor in the pathogenesis of acute immune complex alveolitis in the rat.
Intrapulmonary interleukin-1 beta (IL-1 beta) participates in the pathogenesis of acute IgG immune-complex alveolitis through a mechanism involving neutrophil recruitment. We have examined the relationship between intrapulmonary IL-1 beta and locally produced platelet-activating factor (PAF) in the development of acute alveolitis. Instillation of IgG anti-bovine albumin into the lungs of rats, followed immediately by intravenous infusion of bovine serum albumin (BSA), resulted in acute neutrophil-mediated lung injury. Development of IgG immune-complex lung injury was accompanied by three- and five-fold increases in bronchoalveolar lavage (BAL) fluid and whole lung PAF levels, respectively. Intratracheal administration of the PAF antagonists, WEB-2086 (Boehringer) or L-652,731 (Merck, Sharpe, and Dohme, Rahway, NJ), reduced pulmonary vascular leakage. Neutralization of intrapulmonary IL-1 activity with anti-IL-1 beta antibodies reduced pulmonary vascular permeability and whole lung PAF levels. Morphometric analysis and whole lung myeloperoxidase measurements revealed a differential effect between the PAF antagonists and anti-IL-1 beta with respect to pulmonary neutrophil recruitment. Intratracheal instillation of anti-IL-1 beta retarded net pulmonary neutrophil recruitment while the PAF antagonists retarded migration of neutrophils from the interstitial/vascular compartments into the alveolar compartment. Intratracheal instillation of anti-IL-1 beta plus L-652,731 resulted in reduction in lung vascular permeability and retarded net pulmonary neutrophil recruitment. No additive effect was observed. Stimulation of isolated mouse alveolar macrophages with recombinant murine IL-1 beta or IL-1 alpha resulted in rapid, dose-dependent, and cell concentration-dependent increases in PAF secretion. These data suggest that intrapulmonary IL-1 beta amplifies local PAF production and that IL-1 beta and PAF modulate different aspects of pulmonary neutrophil recruitment.
Warren
J S
JS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
D000208:Acute Disease; D000818:Animals; D000936:Antigen-Antibody Complex; D007375:Interleukin-1 / Q000502:physiology*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010972:Platelet Activating Factor / Q000378:metabolism / Q000502:physiology*; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D011650:Pulmonary Alveoli; D051381:Rats; D011919:Rats, Inbred Strains
D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D010972:Platelet Activating Factor