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Interleukin‐1β and tumour necrosis factor‐α increase microvascular leakage in the guinea pig trachea
Author(s) -
REYNOLDS ANN M.,
HOLMES MARK D.,
SCICCHITANO RAFFAELE
Publication year - 2002
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.2002.00362.x
Subject(s) - extravasation , evans blue , medicine , saline , tumor necrosis factor alpha , guinea pig , necrosis , histamine , anesthesia , pathology
Objective: Airway microvascular leakage is considered to be an important component of airway inflammation in asthma. In the present study we examined the effect of interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNFα) on airway microvascular leakage in vivo . Methodology: Tracheal Evans blue extravasation was examined in an isolated tracheal segment, in anaesthetized mechanically ventilated guinea pigs. Baseline tracheal microvascular leakage was measured in five animals. As a control group for aerosol challenge, the isolated tracheal segment ( n = 5) underwent saline aerosol challenge. To test whether a combination of IL‐1β (10 ng/mL) and TNFα (100 ng/mL) induced Evans blue extravasation, the trachea was exposed to an aerosol of these cytokines ( n = 5). As a positive control the tracheal segment was challenged with histamine aerosol (5 × 10 –2 mol) ( n = 3). All aerosol challenges were for 1 min. Results: TNFα and IL‐1β aerosol challenge significantly increased Evans blue extravasation (28.9 ± 1.6 μg/g wet tissue, mean ± SE) compared to saline challenge (13.8 ± 3.0 μg/g; P < 0.05). Tracheal dye extravasation without aerosol challenge, was not significantly different from saline‐challenged animals (17.5 ± 2.9 and 13.8 ± 3.0 μg/g, respectively). Histamine significantly increased Evans blue extravasation (50.1 ± 4.8 μg/g; P < 0.05) compared to saline challenge. Conclusion: Pro‐inflammatory cytokines, TNFα and IL‐1β are able to induce significant microvascular leakage in the guinea pig trachea.