The effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells.
BACKGROUND
Acute renal failure is a frequent complication of sepsis. Hydroxyethyl starch (HES) is widely used in the treatment of such patients. However, the effect of HES on renal function during sepsis remains controversial. We established an in vitro model of tumor necrosis factor-alpha (TNF-alpha)-stimulated human proximal tubular epithelial (HK-2) cells to assess the possible effects of HES 130/0.42 and HES 200/0.5 on these activated cells.


METHODS
HK-2 cells were stimulated with TNF-alpha in the presence or absence of HES 130/0.42 or 200/0.5. After 4, 10, and 18 h of incubation, monocyte chemoattractant protein-1 (MCP-1), a key chemoattractant for neutrophils and macrophages, was measured. In addition, viability and cytotoxicity assays were performed.


RESULTS
MCP-1 expression was doubled upon TNF-alpha exposure. In the presence of 2% and 4% HES 200/0.5 in 98% (96%) medium over a stimulation time period of 10 h and 18 h, the MCP-1 concentration was decreased between 26% and 56% (P < 0.05). TNF-alpha stimulation resulted in a significant decrease of viability by 53%-63%, whereas viability decreased by only 32%-40% in coincubation with HES 130/0.42 (P < 0.005) and remained even less affected by TNF-alpha in the presence of HES 200/0.5 (P < 0.001). The TNF-alpha-induced cell death rate was attenuated in the presence of HES 200/0.5 (P < 0.05).


CONCLUSIONS
This in vitro study shows that both HES products modulate cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200/0.5 group than for HES 130/0.42, suggesting a possible biological difference between the HES types.
Wittlinger
Moritz
M
Institute of Anesthesiology, University of Zurich, Zurich, Switzerland.
Schläpfer
Martin
M
De Conno
Elisena
E
Z'graggen
Birgit Roth
BR
Reyes
Livia
L
Booy
Christa
C
Schimmer
Ralph C
RC
Seifert
Burkhardt
B
Burmeister
Marc-Alexander
MA
Spahn
Donat R
DR
Beck-Schimmer
Beatrice
B
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005780:Gelatin / Q000494:pharmacology; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation; D007552:Isotonic Solutions / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018613:Microscopy, Confocal; D010952:Plasma Substitutes / Q000494:pharmacology*; D000077325:Ringer's Lactate; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D005456:Fluorescent Dyes; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D000077325:Ringer's Lactate; D014409:Tumor Necrosis Factor-alpha; D005780:Gelatin; C042021:physiogel; D007770:L-Lactate Dehydrogenase; D016650:Fluorescein-5-isothiocyanate