Involvement of tumor necrosis factor-α, interleukin-1β, interleukin- 8, and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction

Sumitaka Imamura, Akihiro Matsukawa, Susumu Ohkawara, Motoko Kagayama, Masaru Yoshinaga

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

A local Shwartzman reaction (LSR) was prepared in rabbit lung as a model of acute lung injury. To induce LSR, intratracheal injection of lipopolysaccharide (LPS) 10 μg into the lower lobe of the right lung, followed 24 h later by i.v. injection of LPS (10 μg/kg). In the lung with the LSR, myeloperoxidase activity, representing neutrophil accumulation, peaked at 1-2 h and was sustained for 48 h after challenge with i.v. LPS. The lung water content peaked at 12 h, and decreased gradually. Histological findings showed diffuse interstitial widening, intra-alveolar leukocyte infiltration with hemorrhage, and alveolar exudate formation. The production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin- 8 (IL-8), and IL-1 receptor antagonist (IL-1Ra) in the lung was analyzed. TNF-α first elevated and peaked at 0.5h (66.5 ± 16.7 ng/g·lung), subsequently, IL-1β and IL-8 increased and peaked at 2h (17.8±3.4ng/g·lung and 336.9±49.6ng/g·lung, respectively). IL-1Ra was present even before the challenge, and the production Increased to show a dual peak (0.5h, 1.5±0.2 μg/g·lung; and 2h, 1.6 ± 0.1 μg/g·lung), and a large concentration of IL-1Ra was sustained for 48 h. Immunohistochemistry showed that the cellular source of these cytokines was alveolar macrophages and infiltrating neutrophils. Thus, disclosing the kinetics of the generation of cytokines led to a better understanding of their roles, namely TNF-α as an initiator, IL- 1 and IL-8 as amplifier and effector, and IL-1Ra as regulator of the intensity of acute inflammation.

Original languageEnglish
Pages (from-to)16-24
Number of pages9
JournalPathology International
Volume47
Issue number1
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

Keywords

  • Shwartzman reaction
  • acute lung injury
  • adult respiratory distress syndrome
  • interleukin- 1β
  • interleukin-1 receptor antagonist
  • interleukin-8
  • tumor necrosis factor-α

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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