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Involvement of tumor necrosis factor‐α, interleukin‐I β, interleukin‐8, and interleukin‐I receptor antagonist in acute lung injury caused by local Shwartzman reaction
Author(s) -
Imamura Sumitaka,
Matsukawa Akihiro,
Ohkawara Susumu,
Kagayama Motoko,
Yoshinaga Masaru
Publication year - 1997
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.1997.tb04430.x
Subject(s) - lung , tumor necrosis factor alpha , interleukin , interleukin 1 receptor antagonist , pathology , receptor antagonist , medicine , infiltration (hvac) , lipopolysaccharide , receptor , chemistry , immunology , cytokine , antagonist , materials science , composite material
A local Shwartzman reactlon (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. injectlon 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 widenlng, lntra‐alveolar leukocyte infiltration with hemorrhage, and alveolar exudate formation. The production of tumor necrosis factor‐α (TNF‐α), interleukin‐1 β (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.±16.7ng/g.lung), subsequently, 11–1β and 11–8 increased and peaked at 2h (17.8 ± 3.4 ng/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 (0.5 h, 1.5±0.2 μg/g.lung; and 2h, 1.6±0.1 μg/g.lung), and a large concentration of IL‐1 Ra was sustained for 48 h. lmmunohistochemistry 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 thelr roles, namely TNF‐α as an initiator, IL‐1 and IL‐8 as amplitier and effector, and IL‐1 Ra as regulator of the intensity of acute inflammation.