Removal of increased circulating CD4+CD25+Foxp3+ regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers

Abstract

Background: Although sepsis-induced immunosuppression has long been considered to be a factor in the late mortality of patients with sepsis, little is known about regulatory T cell (Treg)-mediated immunosuppression and the effect of polymyxin B-immobilized fiber (PMX-F) on sepsis-induced immunosuppression. We sought to investigate the role of CD4(+)CD25(+)Foxp3(+) Tregs in septic patients, and to evaluate the effect of hemoperfusion with PMX-F on the recovery from immunosuppression owing to septic shock.

Methods: Thirty-two septic patients who had an identified focus of infection in the abdominal cavity were enrolled in this study. Peripheral blood mononuclear cells in the septic patients were examined to evaluate the roles of Tregs and the serum cytokine levels. We also examined the effects of PMX-F therapy on CD4(+) T cells, especially Tregs and serum cytokine levels in patients with septic shock.

Results: The percentage of Tregs in the CD4(+) T-cell population, and the serum IL-6 and IL-10 levels, were significantly higher among patients with septic shock compared with those without septic shock, and PMX-F therapy significantly decreased the number of Tregs, as well as the serum IL-6 and IL-10 levels. Furthermore, a significant increase in the number of CD4(+) T cells, a significant decrease in the percentage of Tregs in the CD4(+) T-cell population, and a significant decrease in the serum IL-6 and IL-10 levels 24 hours after PMX-F therapy were observed in septic shock survivors compared with nonsurvivors.

Conclusion: We found a major increase in the percentage of Tregs in peripheral blood circulating CD4(+) T cells from patients with septic shock, and observed that the removal of Tregs by hemoperfusion with PMX-F might represent a novel strategy for inducing recovery from the immunosuppression associated with sepsis.