Background IL33, a member of the IL-1 superfamily has been implicated in the pathogenesis of asthma and postulated to play an aetiological role in several non-pulmonary fibrotic diseases. IL-33 expression has predominantly been reported in mucosal surfaces. We hypothesised lung epithelium might act as a source of IL33 release into the microenvironment as a damage associated molecular pattern (DAMP); propagating pro-inflammatory/fibrotic pathways.

We evaluated tissue expression of IL-33 from a range of chronic lung diseases and assessed release in response to airway epithelial damage in vitro. Finally, we determined if IL-33 was detectable in BAL of lung transplant patients developing Bronchiolitis Obliterans Syndrome (BOS).

Methods Expression of IL-33 in chronic lung disease was evaluated by immunohistochemistry from patients with IPF(n=3), COPD(n=3), Bronchiectasis(n=3) and CF(n=3). Epithelial damage was induced in Primary Bronchial Epithelial Cells and 16HBE14o- cells by oxidative stress or freeze/thaw and release of IL33 evaluated by ELISA and Western Blot. BAL was prospectively collected(n=207) from post lung transplant patients(n=26) and IL-33 concentration measured by ELISA. BAL samples were classified as Non –BOS(n=116) or BOS(n=91) on the basis of histological and clinical data. Co-existing presence of infection was identified by standard microbiological culture.

Results IL33 was strongly expressed in airway epithelia with a predominant nuclear location. This was more marked in chronic lung diseases with an infective aetiology (CF and bronchiectasis). IL33 was not detectable in response to airway epithelial cell injury in vitro. However, IL-33 levels were elevated in BAL of individuals with BOS(p=0.011). Longitudinal analysis of 26 individuals spanning the time frame of initial BOS diagnosis demonstrated a trend towards increased concentration of IL-33 in BAL in the immediate period following BOS diagnosis. There was a strong association between elevated IL-33 levels and the presence of BOS with concomitant infection(p<0.001).

Conclusion IL33 is strongly expressed in the airway epithelium in chronic respiratory diseases but does not appear to be passively released as a DAMP in airway epithelial cell damage. Elevated IL33 with infection in the post transplant population suggests sources other than epithelium may be important but further work is required to evaluate the relevance and significance of these observations.