HEMOFILTRATION IN HUMAN SEPSIS - EVIDENCE FOR ELIMINATION OF IMMUNOMODULATORY SUBSTANCES

Continuous hemofiltration is widely used for renal replacement therapy in patients with acute renal failure. It has been suggested that hemo filtration may also eliminate toxic mediators thought to be important in the pathophysiology of sepsis, The present study examined whether h emofiltration can activate or eliminate inflammatory mediators in pati ents with sepsis, and whether ultrafiltrate can alter specific functio ns of peripheral blood mononuclear leukocytes (PBMC) in vitro. Veno-ve nous hemofiltration was performed in 16 patients and in 5 healthy volu nteers. Pre-filter (afferent), post-filter (efferent) and ultrafiltrat e concentrations of cytokines (IL-1 beta, IL-6, IL-8, TNF alpha) and o f complement components (C3, C3a(desArg), C5a(desArg), terminal comple ment complex) were measured after the beginning of hemofiltration (t(0 )), and 60 minutes later (t(60)). PBMC, and monocyte and lymphocyte su bfractions were incubated with ultrafiltrate, and cytokines were deter mined in the supernatants. Hemofiltration did not induce significant m ediator activation. There was no evidence for significant cytokiine el imination. However, pre-filter C3a(desArg) concentration showed a sign ificant decline during hemofiltration (patients: t(0) = 676.9 +/- 99.7 ng/ml, t(60) = 545.4 +/- 83.2, P < 0.001; volunteers: t(0) = 54.8 +/- 13.3 ng/ml, t(60) = 33.9 +/- 10.7, P < 0.001). Ultrafiltrate from sep tic patients significantly stimulated PBMC and monocyte TNF alpha rele ase, but suppressed lymphocyte IL-2 and IL-6 production. Ultrafiltrate from volunteers was without effect. Hemofiltration effectively elimin ates certain mediators such as C3a(desArg). Ultrafiltrate contains com pounds with significant immunomodulatory qualities. Therefore, hemofil tration may represent a new modality for removal of immunomodulatory m ediators.