Tumour necrosis factor-α and interleukin-10 production in septic patients and the regulatory effect of plasma

Abstract

Objective: To investigate the capacity of patients' whole blood to produce proinflammatory and antiinflammatory cytokines in severe sepsis and to relate abnormalities to the effect of the patients' plasma on cytokine production in healthy donor blood. Design: Open, prospective clinical study. Setting: Teaching hospital, Germany Patients: Ten patients in the surgical intensive care unit with shock and a systemic inflammatory response syndrome (SIRS), a mean APACHE II score of 27, and dysfunction of at least two organ systems at the time of investigation, resulting in 70% mortality. Main outcome measures: Tumour necrosis factor-α (TNF-α) and interleukin-10 (IL- 10) concentrations. Results: TNF-α and IL-10 production of the whole blood in response to lipopolysaccharide (LPS) was reduced from 2 000 pg/ml to 90 pg/ml and from 9163 pg/ml to 622 pg/ml, respectively (p < 0.01). When the plasma of these septic patients was added to the whole blood cells of healthy donors TNF-α production decreased by 38% to 1238 pg/ml (p < 0.01) and IL-10 production by 36% to 5 857 pg/ml (p = 0.03). Conclusion: The effect of plasma from septic patients on the cytokine production in healthy donor blood cells paralleled the decreased production of proinflammatory TNF-α and antiinflammatory IL-10 in the whole blood of septic patients. Efforts to modulate cytokine production in septic patients therefore need to take account of the signals from the plasma as well as the functional capacity of the cells.