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


OBJECTIVE
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.


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.
Stathopoulos
Georgios T
GT
Vanderbilt University School of Medicine, Nashville, Tennessee, USA. gstathop@med.uoa.gr
Sherrill
Taylor P
TP
Karabela
Sophia P
SP
Goleniewska
Kasia
K
Kalomenidis
Ioannis
I
Roussos
Charis
C
Fingleton
Barbara
B
Yull
Fiona E
FE
Peebles
R Stokes
RS
Blackwell
Timothy S
TS
D000230:Adenocarcinoma / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000503:physiopathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D015848:Interleukin-5 / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D008175:Lung Neoplasms / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016066:Pleural Effusion, Malignant / Q000139:chemically induced / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology*
D015848:Interleukin-5