Host-derived Interleukin-5 Promotes Adenocarcinoma-induced Malignant Pleural Effusion

Rationale IL 5 is a T helper 2 cytokine important in the trafficking and survival of eosinophils Because eosinophils can be found in malignant pleural effusions (MPE) from mice and humans, we asked whether IL 5 is involved in the pathogenesis of MPE Objectives To determine the role of IL 5 in MPE formation Methods The effects of IL 5 on experimental MPE induced in C57BL/6 mice by intrapleural injection of syngeneic lung (Lewis lung cancer [LLC]) or colon (MC38) adenocarcinoma cells were determined using wild type (il5(+/+)) and IL 5-deficient il5(-/-) mice, exogenous administration of recombinant mouse (rm) IL 5, and in vivo anti body mediated neutralization of endogenous IL 5 The direct effects of rmIL 5 on LLC cell proliferation and gene expression in vitro were determined by substrate reduction and microarray Measurements and Main Results Eosinophils and IL 5 were present in human and mouse MPE, but the cytokine was not detected in mouse (LLC) or human (A549) lung and mouse colon (MC38) adenocarcinoma conditioned medium, suggesting production by host cells in MPE Compared with il5(+/+) mice, il5(-/-) mice showed markedly diminished MPE format ion in response to both LLC and MC38 cells Exogenous IL 5 promoted MPE formation in il5(+/+) and il5(-/-) mice, whereas anti-IL 5 antibody treatment limited experimental MPE in il5(+/+) mice Exogenous IL 5 had no effects on LLC cell proliferation and gene expression, however, IL 5 was found to be responsible for recruitment of eosinophils and tumor promoting myeloid suppressor cells to MPE in vivo Conclusions Host derived IL 5 promotes experimental MPE and may be involved in the pathogenesis of human MPE