title: Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis.
abstract: Acute 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.
authors.affiliation: The Department of Respiratory Medicine, NHO Yamaguchi-Ube Medical Center, Ube 755-0241, Japan. ohishk@yamaguchi-hosp.jp
authors.forename: Keiji
authors.initials: K
authors.lastname: Oishi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mimura-Kimura
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ogata
authors.forename: Hideki
authors.initials: H
authors.lastname: Katayama
authors.forename: Yoriyuki
authors.initials: Y
authors.lastname: Murata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mimura
mesh_terms: D000368:Aged; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D005260:Female; D006464:Hemoperfusion; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D011112:Polymyxin B / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D011112:Polymyxin B