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

Objective: To investigate the capacity of patients' whole blood to produce proinflammatory and antiinflammatory cytokines in severe sepsis and to rela te abnormalities to the effect of the patients' plasma on cytokine producti on 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 investigat ion, resulting in 70% mortality. Main outcome measures: Tumour necrosis factor-alpha (TNF-alpha) and interle ukin-10 (IL-10) concentrations. Results: TNF-alpha and IL-10 production of the whole blood in response to l ipopolysaccharide (LPS) was reduced from 2000 pg/ml to 90 pg/ml and from 9 163 pg/ml to 622 pg/ml, respectively (p < 0.01). When the plasma of these s eptic patients was added to the whole blood cells of healthy donors TNF-alp ha production decreased by 38% to 1 238 pg/ml (p < 0.01) and IL-10 producti on by 36% to 5 857 pg/ml (p = 0.03). Conclusion: The effect of plasma from septic patients on the cytokine produ ction in healthy donor blood cells paralleled the decreased production of p roinflammatory TNF-alpha and antiinflammatory IL-10 in the whole blood of s eptic patients. Efforts to modulate cytokine production in septic patients therefore need to take account of the signals from the plasma as well as th e functional capacity of the cells.