Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion.

Stathopoulos GT, Sherrill TP, Karabela SP, Goleniewska K, Kalomenidis I, Roussos C, Fingleton B, Yull FE, Peebles RS, Blackwell TS
Am J Respir Crit Care Med. 2010 182 (10): 1273-81

PMID: 20595227 · PMCID: PMC3001265 · DOI:10.1164/rccm.201001-0001OC

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 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 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 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.

CONCLUSIONS - Host-derived IL-5 promotes experimental MPE and may be involved in the pathogenesis of human MPE.

MeSH Terms (14)

Adenocarcinoma Animals Carcinoma, Lewis Lung Cell Line, Tumor Dose-Response Relationship, Drug Eosinophils Flow Cytometry Gene Expression Profiling Humans Interleukin-5 Lung Neoplasms Mice Mice, Inbred C57BL Pleural Effusion, Malignant

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