title: Apheresis of activated leukocytes with an immobilized polymyxin B filter in patients with septic shock.
abstract: In this study, we examined the effects of direct hemoperfusion through filters with immobilized polymyxin B (PMX-DHP) on leukocyte function and plasma levels of cytokines in patients with septic shock. We found that PMX-DHP caused increased expression of C-X-C chemokine receptor 1 (CXCR1) and CXCR2, along with decreased expression of CD64 and CD11b, by circulating neutrophils in patients with septic shock. Plasma levels of cytokines, including interleukin 6 (IL-6), IL-8, IL-10, and high-mobility group box 1, were elevated in patients with septic shock compared with healthy controls, but cytokine levels were not altered by PMX-DHP. These results suggest that PMX-DHP influences neutrophils via a mechanism that does not involve cytokine. Ex vivo perfusion of heparinized blood from patients with sepsis and septic shock through PMX filters in a laboratory circuit caused a significant decrease in neutrophil and monocyte counts. After 120 min of perfusion, neutrophils, monocytes, and lymphocytes were decreased by 78%, 70%, and 10%, respectively, compared with baseline values. Flow cytometric analysis indicated that activated neutrophils with high levels of CD11b/CD64 expression and low levels of CXCR1/CXCR2 expression showed preferential adhesion to PMX filters. Neutrophils isolated from the blood after ex vivo PMX perfusion caused less damage to an endothelial cell monolayer than cells from sham-treated blood, whereas neutrophil phagocytosis of opsonized Escherichia coli was unaffected. These results indicate that PMX-DHP selectively removes activated neutrophils and reduces the ability of circulating cells to cause endothelial damage. Selective removal of activated neutrophils using PMX-DHP may improve the systemic inflammatory response in patients with septic shock.
authors.affiliation: Department of Emergency & Critical Care Medicine, Aichi Medical University, Nagakute, Aichi, Japan. kuma@aichi-med-u.ac.jp
authors.forename: Tuneyasu
authors.initials: T
authors.lastname: Kumagai
authors.forename: Naoshi
authors.initials: N
authors.lastname: Takeyama
authors.forename: Teru
authors.initials: T
authors.lastname: Yabuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Harada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miki
authors.forename: Hideki
authors.initials: H
authors.lastname: Kanou
authors.forename: Sousuke
authors.initials: S
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
mesh_terms: D055371:Acute Lung Injury / Q000517:prevention & control; D000368:Aged; D000954:Antigens, Surface / Q000032:analysis; D002478:Cells, Cultured / Q000473:pathology; D016207:Cytokines / Q000097:blood; D042783:Endothelial Cells / Q000473:pathology; D004926:Escherichia coli; D005260:Female; D005374:Filtration / Q000295:instrumentation*; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000097:blood; D006464:Hemoperfusion / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007937:Leukapheresis / Q000295:instrumentation* / Q000379:methods; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D011112:Polymyxin B; D012772:Shock, Septic / Q000097:blood / Q000276:immunology / Q000628:therapy*
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D024243:HMGB1 Protein; D009895:Opsonin Proteins; D011112:Polymyxin B