• Keiji Oishi, Yuka Mimura-Kimura, Taku Miyasho, Keisuke Aoe, Yoshiko Ogata, Hideki Katayama, Yoriyuki Murata, Hiroshi Ueoka, Tsuneo Matsumoto, and Yusuke Mimura.
• The Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center, Ube 755-0241, Japan. ohishk@yamaguchi-hosp.jp
• Cytokine. 2013 Jan 1; 61 (1): 84-9.

AbstractAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is characterized by severe worsening dyspnea of unknown etiology and high mortality without effective treatment. Recently, direct hemoperfusion with polymyxin B (PMX)-immobilized fiber cartridge (PMX-DHP) has been reported to improve pulmonary oxygenation and survival in patients with AE-IPF although its mechanism of action remains unknown. To gain insights into the pathobiology of AE-IPF through the beneficial effects of PMX-DHP, we analyzed the profile of cytokines adsorbed onto PMX-fibers used in 9 AE-IPF patients. In addition, the sera of these AE-IPF patients collected immediately before and after PMX-DHP, 9 stable IPF patients and 8 healthy individuals were also analyzed. The serum levels of cytokines including IL-9, IL-12, IL-17, PDGF and VEGF were significantly decreased immediately after PMX-DHP (P<0.02), and VEGF and IL-12 were most prominently reduced. In addition to PDGF and VEGF, IL-1β, IL-1ra, IL-8, IL-23, FGF basic, GM-CSF, IP-10, RANTES and TGF-β were eluted from used PMX-fibers. Interestingly, improved pulmonary oxygenation after PMX-DHP was correlated well with the quantities of eluted VEGF. These results suggest that adsorption of proinflammatory, profibrotic and proangiogenic cytokines onto PMX-fibers is one of the mechanisms of action of PMX-DHP in AE-IPF. Notably, removal of VEGF by PMX-DHP may contribute to the rapid improvement in oxygenation by suppressing vascular permeability in the lung.Copyright © 2012 Elsevier Ltd. All rights reserved.

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