Improvement of Monocyte Secretion Function in a Porcine Pancreatitis Model by Continuous Dose-Dependent Veno-Venous Hemofiltration

Abstract

Objective

Monocyte and its secreted cytokines play a crucial role in the process of severe acute pancreatitis (SAP). It has been known that continuous veno-venous hemofiltration (CVVH) can partially attenuate the inflammatory process by removal of cytokines, but the effect of CVVH on monocyte secretion function remains unknown. This study investigated the effect of different doses of CVVH on monocyte secretion function as well as the plasma cytokine profile in a SAP porcine model.

Methods

After successful induction of SAP by pressure-controlled (100 mmHg), intraductal injection of sodium taurocholate (4%, 1 ml/kg) and trypsin (2 U/kg), 24 swine were randomly assigned to 3 groups. Swine in group I (n=8) serving as SAP controls received only standard medical therapy (SMT). Besides SMT, swine in two other groups received zero-balanced CVVH, one hour after the induction of SAP, with low volume fluid exchange (group II, n=8, ultrafiltration rate (UFR) 20 ml/kg/h, LV-CVVH) or high volume (group III, n=8, UFR 100 ml/kg/h, HV-CVVH). Using heparin as anticoagulant, the filter (AN69, Hospal, Lyon, France) was changed every 24 hours. Monocytes were isolated from porcine blood at various timepoints for detection of cytokine secretion (interleukin-6, IL-6; interleukin-10, IL-10; tumor necrosis-α, TNF-α) after LPS stimulus; plasma cytokines were measured simultaneously.

Results

CVVH showed a dose-dependent beneficial effect on the animals’ survival time. In control animals, plasma pro-inflammatory cytokine levels exhibited a double-phase fluctuation after SAP induction: IL-6 and TNF-α rapidly increased to a peak level within 6–12 hours, then dropped to very low level in the late stage. Unlike pro-inflammatory cytokines, the plasma level of anti-inflammatory cytokine IL-10 reached a plateau within 6–12 hours but dropped little. In CVVH-treated animals, the peak-nadir patterns of 3 cytokines were all flattened, most prominently in the HV-CVVH group. Similarly to plasma cytokine patterns, the monocyte ex vivo response to LPS stimulus showed an over-production of cytokines within 6–12 hours, but low production in the late stage. Although unable to totally prevent the abnormality of the monocyte secretion function, CVVH showed a dose-dependent ameliorative effect on it.

Conclusions

Monocytes are over-reactive to stimulus in the early stage of SAP, accompanied by a high level of plasma cytokines, and hypo-reactive to stimulus in the late stage of SAP, accompanied with a low level of plasma cytokines. CVVH treatment has a dose-dependent improvement effect on monocyte responsiveness.

Keywords

Severe acute pancreatitis Continuous veno-venous hemofiltration Cytokines Monocytes

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