title: Proinflammatory cytokines are not released in the circulation following acute pulmonary thromboembolism in pigs.
abstract: Histological examination of acute lung injury associated with sepsis often revealed thromboembolic lesions in the pulmonary microcirculation. Several inflammatory mediators such as platelet activating factor, thromboxane, and endothelins have also been implicated in the pathogenesis of acute pulmonary thromboembolism (APTE). In the present study we examined the roles of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-8, in the early phase of APTE. APTE was induced in 13 anesthetized piglets (22+/-4 kg) by injecting thrombin-induced blood clots directly into the left lower lobar pulmonary artery. Five animals that received only warm sterile saline served as controls. Arterial plasma samples were collected regularly over 8 h so that cytokine levels could be measured later by enzyme-linked immunosorbent assay (ELISA). Administration of clots doubled the mean pulmonary arterial pressure (from 13+/-5 to 26+/-7 mm Hg) and caused significant decrease in arterial oxygen tension (PaO2 from 390+/-85 to 256+/-89 mm Hg while the FiO2 was maintained at 1.0). Mean arterial blood pressure and cardiac output remained comparable throughout the experiments after initial fluid resuscitation. Plasma levels of TNF-alpha, IL-1beta, and IL-8 were not significantly increased in the APTE group when compared with their baseline values or the control group. Our results thus show that APTE is associated with pulmonary hypertension and deterioration of gas exchange but not with the systemic release of TNF-alpha, IL-1beta, or IL-8. We conclude that these cytokines have minimal impact on the systemic circulation during APTE.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. jtsang@interchange.ubc.ca
authors.forename: John
authors.initials: J
authors.lastname: Tsang
authors.forename: Mathieu
authors.initials: M
authors.lastname: Simon
authors.forename: Ken
authors.initials: K
authors.lastname: Stewart
authors.forename: Karim
authors.initials: K
authors.lastname: Qayumi
authors.forename: Bruno
authors.initials: B
authors.lastname: Battistini
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000503:physiopathology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha