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.
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 mousecolon (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.
Authors: M A Martínez-García; E Cases-Viedma; P J Cordero-Rodríguez; M Hidalgo-Ramírez; M Perpiñá-Tordera; F Sanchis-Moret; J L Sanchis-Aldás Journal: Eur Respir J Date: 2000-01 Impact factor: 16.671
Authors: J A Burgers; P W A Kunst; M G J Koolen; L N A Willems; J S Burgers; M van den Heuvel Journal: Eur Respir J Date: 2008-07-09 Impact factor: 16.671
Authors: Allyson G McLoed; Taylor P Sherrill; Dong-Sheng Cheng; Wei Han; Jamie A Saxon; Linda A Gleaves; Pingsheng Wu; Vasiliy V Polosukhin; Michael Karin; Fiona E Yull; Georgios T Stathopoulos; Vassilis Georgoulias; Rinat Zaynagetdinov; Timothy S Blackwell Journal: Cell Rep Date: 2016-06-16 Impact factor: 9.423
Authors: Anastasios D Giannou; Antonia Marazioti; Magda Spella; Nikolaos I Kanellakis; Hara Apostolopoulou; Ioannis Psallidas; Zeljko M Prijovich; Malamati Vreka; Dimitra E Zazara; Ioannis Lilis; Vassilios Papaleonidopoulos; Chrysoula A Kairi; Alexandra L Patmanidi; Ioanna Giopanou; Nikolitsa Spiropoulou; Vaggelis Harokopos; Vassilis Aidinis; Dionisios Spyratos; Stamatia Teliousi; Helen Papadaki; Stavros Taraviras; Linda A Snyder; Oliver Eickelberg; Dimitrios Kardamakis; Yoichiro Iwakura; Thorsten B Feyerabend; Hans-Reimer Rodewald; Ioannis Kalomenidis; Timothy S Blackwell; Theodora Agalioti; Georgios T Stathopoulos Journal: J Clin Invest Date: 2015-04-27 Impact factor: 14.808
Authors: Konstantinos Doris; Sophia P Karabela; Chrysoula A Kairi; Davina Cm Simoes; Charis Roussos; Spyros G Zakynthinos; Ioannis Kalomenidis; Timothy S Blackwell; Georgios T Stathopoulos Journal: Respir Res Date: 2010-08-26