Differential expression of IL-33 and HMGB1 in the lungs of stable cystic fibrosis patients

To the Editor: In cystic fibrosis (CF), repeated inflammation of the lung leads to progressive damage of lung tissue [1, 2]. In case of tissue destruction or in response to inflammation, necrotic cells release danger signals. These proteins trigger inflammatory responses, contribute to elimination of pathogens and induce tissue repair [3]. Imbalanced or uncontrolled release of such mediators may amplify inflammatory responses that in turn facilitate tissue damage. Interleukin (IL)-33 and high-mobility group box 1 protein (HMGB1) are both considered to be such “alarmins” [3]. Given the T-helper cell (Th)17/Th2 nature of lung inflammation in asymptomatic CF individuals and its linkage to CF-associated pathogens [1, 2], we hypothesised that IL-33 and HMGB1 may contribute to the local sustained inflammatory processes. Both these alarmins are dual-function proteins, as they are nuclear factors regulating gene expression and also act as cytokines when released from cells [3]. In contrast to ubiquitously expressed HMGB1, IL-33 is mainly expressed in barrier-function-like epithelial cells [3]. IL-33 is mainly linked to augmentation and initiation of Th2-type inflammation but might also antagonise overwhelming tissue inflammation linked to pathogens [4–6]. HMGB1 acts as a cytokine, which contributes to activation of innate receptors, matures dendritic cells (DCs), contributes to migration of DCs and amplifies inflammation itself via induction of pro-inflammatory cytokines like tumour necrosis factor (TNF)-α, IL-6, IL-1β and macrophage inflammatory protein (MIP)1 [7]. To directly compare the contributions of released IL-33 and HMGB1 in CF lung inflammation, we assessed protein levels in bronchoalveolar lavage fluid (BALF) of 44 CF patients and 10 non-CF controls with recurrent pulmonary infections. To increase the homogeneity of the CF population, patients with …