Modulation of Polymorphonuclear Leukocyte Apoptosis in the Critically Ill by Removal of Cytokines with Continuous Hemodiafiltration

Abstract

Delay of polymorphonuclear leukocyte (PMN) apoptosis caused by hypercytokinemia is considered to be a potential cause of tissue damage and resultant organ failure. We evaluated whether continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which can remove cytokines in the circulating blood, can modulate apoptosis in peripheral blood neutrophils and thereby reduce tissue damage and organ dysfunction in 25 critically ill patients. Following the completion of a 3-day PMMA-CHDF session, serum cytokine levels were significantly decreased and the percentage of apoptotic PMNs was significantly increased. A significant correlation was observed between the PMMA-CHDF-induced increase in the percentage of apoptotic PMNs and the degree of decrease in the serum interleukin-6 level. A significant correlation was also found between the increase in the percentage of apoptotic PMNs and improvement in sequential organ failure assessment score following PMMA-CHDF. These results suggest that PMMA-CHDF in critically ill patients with hypercytokinemia and concomitant delay in apoptosis of PMNs can alleviate the delay of PMN apoptosis through the removal of serum cytokines and thus may result in avoidance of organ dysfunction.

Continuous Hemodiafiltration with Cytokine-Adsorbing Hemofilter in the Treatment of Severe Sepsis and Septic Shock

“…We found that PMMA-CHDF was able to remove IL-10 and that such a removal of anti-inflammatory cytokines resulted in an improvement in the depressed monocytic HLA-DR expression in septic patients. We also reported that delayed apoptosis of neutrophils, which is an important pathogenesis of organ failure in sepsis, is recovered through the removal of cytokines with PMMA-CHDF [17]. These are the mechanisms of the efficacy of PMMA-CHDF in the treatment of severe sepsis and septic shock.…”

Pilot Investigation of the Association Between Serum Stress Neuropeptide Levels and Lymphocyte Expression of Fas and Fas Ligand in Critical Illness

“…In the future, concomitant quantification of NK Fas/FasL expression along with Annexin-V staining for quantification of apoptosis and functional immune cell response testing may provide further insight. Moreover, although a delay in polymorphonuclear (PMN) apoptosis has been identified in critical illness (Hirano et al, 2004), a link between the Fas/FasL system and PMN counts has not been established in critically ill individuals. The pleiotropic nature of the Fas/FasL system may also need to be addressed in the future.…”

Severe Acute Mountain Sickness Complicated by Multiple Organ Dysfunction Syndrome

“…However, endotoxins delay PMN apoptosis through induced production of inhibitor of apoptosis protein-2 (cIAP-2), which accelerates the degradation of activated caspase-3 [9]. Hirano et al found that the use of technical processing in continuous renal replacement therapy (CRRT) in hemodialysis could significantly improve the delay in neutrophil apoptosis by clearing inflammatory factors (IL-6, IL-8, TNFa) from patients' blood, thereby reducing damage to tissues and organs [10]. This indicates that delays in neutrophil apoptosis may be a major cause of tissue damage.…”