• Georgios T Stathopoulos, Taylor P Sherrill, Sophia P Karabela, Kasia Goleniewska, Ioannis Kalomenidis, Charis Roussos, Barbara Fingleton, Fiona E Yull, R Stokes Peebles, and Timothy S Blackwell.
• Vanderbilt University School of Medicine, Nashville, Tennessee, USA. gstathop@med.uoa.gr
• Am. J. Respir. Crit. Care Med. 2010 Nov 15; 182 (10): 127312811273-81.

RationaleIL-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.ObjectivesTo determine the role of IL-5 in MPE formation.MethodsThe 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 antibody-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 ResultsEosinophils 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 formation 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.ConclusionsHost-derived IL-5 promotes experimental MPE and may be involved in the pathogenesis of human MPE.

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