Interleukin-1beta and tumour necrosis factor-alpha increase microvascular leakage in the guinea pig trachea

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-1beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha) on airway microvascular leakage in vivo.

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-1beta (10 ng/mL) and TNFalpha (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 x 10(-2) mol) (n = 3). All aerosol challenges were for 1 min.

TNFalpha and IL-1beta aerosol challenge significantly increased Evans blue extravasation (28.9 +/- 1.6 microg/g wet tissue, mean +/- SE) compared to saline challenge (13.8 +/- 3.0 microg/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 microg/g, respectively). Histamine significantly increased Evans blue extravasation (50.1 +/- 4.8 microg/g; P < 0.05) compared to saline challenge.

Pro-inflammatory cytokines, TNFalpha and IL-1beta are able to induce significant microvascular leakage in the guinea pig trachea.