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It was assumed that pathologic activation of neutrophils and monocytes is associated with sepsis, acute lung injury/ARDS, and multiple organ failure, and that removal of these cells from the circulation could reduce leukocyte-dependent tissue injury. Cartridges containing polymyxin B (PMX) immobilized to fibers (Toraymyxin; Toray Industries, Tokyo, Japan) have been developed for selective adsorption of circulating endotoxin in patients with Gram-negative bacterial infection, and this treatment has proven to be highly effective. This study examined the effect of direct hemoperfusion through filters with immobilized PMX direct-hemoperfusion (DHP) on leukocyte function and plasma levels of cytokines in patients with septic shock.
We evaluated the effect of PMX-DHP on circulating leukocytes in patients with septic shock by assessing the changes of neutrophil and monocyte surface antigen expression after PMX-DHP. In another experiment, heparinized blood from patients with sepsis was passed through PMX filters in a laboratory circuit and then changes of the cell count and surface antigen expression by neutrophils and monocytes were assessed. After perfusion, neutrophils were isolated and the capacity of these cells to damage cultured endothelial monolayers was also determined.
We found that PMX-DHP led to an increased CXCR1 and CXCR2 expression along with a decrease of CD64 and CD11b expression by circulating neutrophils from septic patients. Plasma levels of cytokines, including 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. Ex vivo perfusion of heparinized blood from patients with sepsis through PMX filters in a laboratory circuit caused a significant decrease of the neutrophil and monocyte counts. Activated neutrophils with high CD11b/CD64 expression and low CXCR1/CXCR2 expression showed preferential adhesion to PMX filters. Neutrophils isolated from the blood after ex vivo PMX perfusion caused less damage on the endothelial cell monolayer than cells from sham-treated blood.
PMX-DHP influences neutrophils via a mechanism that does not involve cytokines. Ex vivo 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 by PMX-DHP may contribute to improvement of the systemic inflammatory reaction in septic patients.