THE INFLUENCE OF COLLOIDAL PLASMA SUBSTIT UTES ON THE RELEASE OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN HUMAN WHOLE-BLOOD IN-VITRO

Objective: To investigate the influence of colloidal plasma substitute s on human cytokine network, especially of tumor necrosis factor alpha (TNF-alpha), in vitro. Design: Heparinized whole blood samples from 8 healthy volunteers were divided and set on various concentrations of artificial colloidal plasma substitutes (native = 0 mg/ml; 5 mg/ml; 15 mg/ml). As colloids were used hydroxyethyl starch 200/0,5 (HES), dext ran 60 (DX), urea-linked gelatin (GEL) and human albumin solution (HA) . After incubation (24 h; 5% CO2; 37 degrees C; with and without conco mitant stimulation of blood cells with phytohemagglutinin [PHA]) measu rement of TNF-alpha release was performed via ELISA by the method desc ribed by Gallati. For the statistical evaluation a repeated measures a nalysis of variance was used. Results: Basic level of TNF-alpha was fo und between 226 and 273 pg/ml (0 mg of each colloid/ml), stimulation w ith PHA without any colloid increased the TNF-alpha level about fourfo ld (1,066-1,260 pg/ml; 0 mg of each colloid/ml). At 5 mg/ml and 15 mg/ ml without PHA all 3 artificial colloids rose the level of TNF-alpha ( up to 50%). Under concomitant stimulation each colloid induced additio nal TNF-alpha release in comparison to PHA alone. The changes elicited by DX and GEL were statistically significant (p<0.001 and p=0.005, re spectively) in contrast to those induced by human albumin solution or HES. Conclusion: In relation to TNF-alpha plasma substitutes are not i nert substances as perhaps suspected. The questions whether the observ ed effects exist in vivo, how far other cytokines are influenced and t he question about the clinical importance are subject of ongoing studi es.