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Hemofiltration reduces the serum priming activity on neutrophil chemiluminescence in septic patients
1Department of Area of Medicine, Nephrology and Dialysis Unit, CTO Hospital, Turin, Italy.
Background:
Priming of the polymorphonuclear neutrophil (PMN) response has been implicated in the activation of oxidative burst and tissue injury in patients with septic shock and acute renal failure (ARF). This study evaluated whether hemofiltration (HF) removes substances able to enhance the oxidative burst of PMNs.
Methods:
Chemiluminescence (CL) priming activity induced by sera and ultrafiltrates of seven patients with septic shock, multiorgan dysfunction syndrome, and ARF (ARF/HF group) and of 10 uremic stable patients (Control/HF group) was evaluated on normal human PMNs stimulated with bacterial formyl-methionyl-leucyl-phenylalanine (FMLP). Patients submitted to HF were studied by determining blood and ultrafiltrate interleukin-8 (IL-8), platelet-activating factor (PAF), and CL priming activity at the beginning (T0), and after four hours (T4) of treatment.
Results:
Preincubation of normal human PMNs with sera and ultrafiltrates from septic patients induced a potent priming of CL activity in subsequent FMLP stimulation. In the ARF/HF group, the prefilter blood concentrations of IL-8 and CL PMN-priming activity significantly decreased during the four hours of HF treatment, with a loss of IL-8 in the ultrafiltrate of 6930 (median, range 4292 to 9282) ng per four hours. PAF detected in the ultrafiltrate and associated with the membrane (7.3 ng, range 1.45 to 9.89) was minimal. In the ARF/HF group, a significantly positive correlation between CL PMN-priming activity and IL-8 concentrations was observed. The CL priming activity in blood and ultrafiltrates was reduced to 55 and 46% by preabsorption with monoclonal antibody (mAb) anti-IL-8. In contrast, the PAF receptor antagonist WEB 2170 did not affect CL priming activity. In the control/HF group, the CL PMN-priming activity was significantly lower than in the ARF/HF group and was independent of IL-8.
Conclusions:
Sera from septic patients demonstrate an enhanced CL priming activity on PMNs. This activity is reduced by ultrafiltration and is due, at least in part, to ultrafiltered IL-8.
Insights
Hemofiltration effectively reduces the polymorphonuclear neutrophil (PMN) priming activity in septic patients with acute renal failure (ARF). This reduction is primarily attributed to the removal of interleukin-8 (IL-8), a key inflammatory mediator.
Area of Science:
- Nephrology
- Immunology
- Critical Care Medicine
Background:
- Polymorphonuclear neutrophil (PMN) priming contributes to oxidative burst and tissue injury in septic shock and acute renal failure (ARF).
- The role of hemofiltration (HF) in removing substances that enhance PMN oxidative burst requires investigation.
Purpose of the Study:
- To evaluate if hemofiltration (HF) can remove substances that enhance the oxidative burst of PMNs in patients with ARF.
Main Methods:
- Assessed chemiluminescence (CL) priming activity in sera and ultrafiltrates from ARF patients undergoing HF and a control group.
- Measured blood and ultrafiltrate levels of interleukin-8 (IL-8) and platelet-activating factor (PAF) before and after HF treatment.
Main Results:
- Septic patient sera and ultrafiltrates significantly primed PMN chemiluminescence.
- HF treatment reduced IL-8 concentrations and PMN-priming activity in ARF patients.
- A positive correlation was found between IL-8 levels and PMN-priming activity, which was partially blocked by anti-IL-8 antibodies.
Conclusions:
- Sera from septic patients exhibit enhanced PMN priming activity.
- Hemofiltration reduces this activity, largely due to the removal of ultrafiltered IL-8.
