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

Am J Respir Crit Care Med. 2010 Nov 15;182(10):1273-81. doi: 10.1164/rccm.201001-0001OC. Epub 2010 Jul 1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / physiopathology*
  • Animals
  • Carcinoma, Lewis Lung / complications
  • Carcinoma, Lewis Lung / physiopathology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Eosinophils / physiology
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Interleukin-5 / analysis
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / pharmacology
  • Interleukin-5 / physiology*
  • Lung Neoplasms / complications
  • Lung Neoplasms / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Pleural Effusion, Malignant / chemically induced
  • Pleural Effusion, Malignant / chemistry
  • Pleural Effusion, Malignant / cytology
  • Pleural Effusion, Malignant / physiopathology*

Substances

  • Interleukin-5