Pleural Effusion IL-33/sST2 Levels and Effects of Low and High IL-33/sST2 Levels on Human Mesothelial Cell Adhesion and Migration

Interleukin 33 (IL-33) is an alarmin with multiple roles in immunity and cell homeostasis, highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). Production of IL-33 and soluble ST2 (sST2), a decoy receptor for IL-33, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of IL-33 and sST2 in transudative (TrPEs), malignant (MPEs), and parapneumonic (PPEs) pleural effusions (PEs) and investigate the effect of PE fluids from each group with low and high IL-33/sST2 levels on MeT-5A cell adhesion and migration. IL-33 and sST2 pleural fluid levels were similar among TrPEs, MPEs, and PPEs. However, a significant correlation was found between IL-33 and LDH and in sST2 levels with lymphocyte counts in TrPEs. Additionally, in MPEs the levels of IL-33 correlated with the levels of sST2 and with the red blood cell counts. Furthermore, incubation of MeT-5A cells with MPEs and PPEs bearing low or high levels of IL-33/sST2 yielded significant differential effects on MeT-5A cell adhesion and migration. In MPEs, high IL-33/sST2 levels led to increased adhesion and migration of MeT-5A cells, while in PPEs the effect was the opposite, while no effect in both cell phenotypes was determined for TrPEs. These results reveal a clinical context dependent effect of the IL-33/sST2 axis in PEs.