We hypothesized that cytokine production following delayed in vitro cell stimulation (to reproduce physiological cellular status at baseline) may be related to outcome in patients with septic shock. A total of 20 patients were included in a prospective clinical study, conducted in a medico-surgical intensive care unit in a university hospital. Blood samples were obtained at the onset of septic shock; these were treated to retain the cells, but to wash out autologous plasma (containing potential inflammatory stimuli such as cytokines, bacterial products and drugs) and replace it with foetal calf serum. Each treated sample was divided into two sets of four aliquots, to be stimulated either immediately or after an overnight period of resting incubation at 37°C. The rest period was to allow recovery from potentially reversible endogenous or pharmacologically induced alterations in cellular response, in order to reproduce a near physiological state at baseline. In vitro cellular challenges used low-dose (0.2ng/ml) or high-dose (1ng/ml) CD14-dependent lipopolysaccharide and CD14-independent pokeweed mitogen to induce the production of tumour necrosis factor-α (TNF-α), and interleukins-1β and -10. Levels of TNF-α, interleukin-1β and interleukin-10 were significantly higher (P < 0.05) when cell stimulation was delayed for 16h, indicating a functional down-regulation of cells during septic shock. Moreover, TNF-α responses obtained with high-dose lipopolysaccharide were significantly greater in cells from patients who subsequently survived septic shock (n = 13; median value 1392pg/ml; range 592-2048pg/ml) than in cells from non-survivors (n = 7; median value 708 pg/ml; range 520-1344pg/ml). These observations support the existence of individual differences in the inflammatory response that could influence patient outcome following septic shock.
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March 2002
Research Article|
February 13 2002
Response of tumour necrosis factor-α to delayed in vitro monocyte stimulation in patients with septic shock is related to outcome
Olivier APPOLONI;
Olivier APPOLONI
*Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium
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Jean-Louis VINCENT;
*Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium
Correspondence: Professor Jean-Louis Vincent (e-mail jlvincen@ulb.ac.be).
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Jean DUCHATEAU
Jean DUCHATEAU
†Department of Immunology, Brugmann University Hospital, Free University of Brussels, B-1070 Brussels, Belgium
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Clin Sci (Lond) (2002) 102 (3): 315–320.
Article history
Received:
September 06 2001
Accepted:
October 01 2001
Citation
Olivier APPOLONI, Jean-Louis VINCENT, Jean DUCHATEAU; Response of tumour necrosis factor-α to delayed in vitro monocyte stimulation in patients with septic shock is related to outcome. Clin Sci (Lond) 1 March 2002; 102 (3): 315–320. doi: https://doi.org/10.1042/cs1020315
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