Frank et al have elegantly demonstrated in animal models of ventilator associated lung injury (VALI) that interleukin 1β (IL1β) may play a role in the development of alveolar barrier dysfunction. However, the ventilation strategy used for these experiments (with a very high tidal volume of 30 ml/kg) induced an increase in IL1β of only 36 pg/ml in lavage as opposed to 7 pg/ml in their control animals, a level that in their in vitro models of epithelial resistance and permeability did not significantly affect permeability.1

Our recent study published in Thorax has evaluated IL1β levels in bronchoalveolar lavage fluid in patients with adult respiratory distress syndrome (ARDS) as 143 pg/ml.2 Thus their animal model does not adequately reflect the in vivo situation in patients with established ARDS. We believe this may be important because several lines of evidence suggest that IL1β may play a role in stimulating repair of the alveolar epithelium.

Effective alveolar repair following the development of ARDS is believed to involve the transdifferentiation of alveolar type II cells (ATII), which retain stem cell-like properties, into type I cells via intermediate cell phenotypes. The turnover rate of ATII cells is boosted after acute lung injury and the recovery process is believed to involve cell migration and proliferation in addition to transdifferentiation of ATII epithelial cells.3

Geiser et al were the first to show that pulmonary oedema fluid, early in the course of ARDS, stimulates repair of wounded monolayers in culture to a greater extent than plasma obtained from the same patients or pulmonary oedema fluid from patients with hydrostatic oedema.4 The potential of oedema fluid to promote wound repair was associated with a trend towards improved survival and reduction in the duration of ventilation. The enhanced wound repair is IL1β dependent and mediated by autocrine release of epidermal growth factor and transforming growth factor α.5 Recently, we have further demonstrated that lung lavage fluid from ARDS patients treated with intravenous salbutamol enhanced A549 monolayer wound repair responses compared with placebo treated patients in vitro by an IL1β dependent mechanism.2

In conclusion, the data from the study by Frank et al clearly demonstrate that increased IL1 signalling may be an early mechanism of alveolar barrier dysfunction in VALI in rats and mice. However, significant evidence suggests that once ARDS is established, elevated IL1 levels may have beneficial effects on epithelial repair. We believe that this may therefore account for the apparent failure of anti-IL1 strategies in humans with ARDS.