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Development of a cell culture model for septic shock multiorgan failure

T. Hartung and A. Wendel
Lehrstuhl für Biochemische Pharmakologie, Universität D-Konstanz
Summary

Septic shock remains a clinical problem difficult to manage. Several animal models have been established which closely reflect symptoms and course of septic shock. Regarding therapeutic approaches, the possibilities pharmacological intervention are unsatisfactory and call for further investigation. By now, the induction of multiorgan failure in experimental animals has been considered as a successful approach. These experiments impose considerable suffering to animals. The complexity of the molecular events taking place in vivo further restricts the possibility to define rationales for therapeutic intervention. These two aspects prompted the development of a cell-culture model which shares basic mechanisms with the whole-animal experiment. In this cell model using the coculture of parenchymal and non-parenchymal rat-liver cells, endotoxins, i.e. compounds from bacterial cell walls, induce an acute hepatocyte damage. Data obtained with the cell-culture model system are summarised in order to validate the cell-model in comparison to animal pathology, i.e. septic liver failure. Major mechanistic analogies offer the opportunity to develop a useful alternative to animal experiments in the field of septic shock.

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