A CONTROLLED-STUDY OF LEUKOCYTE ACTIVATION IN SEPTIC PATIENTS

Objective: Qualitative and quantitative evaluation of leukocyte activa tion in septic patients in comparison to two control groups. Design: A prospective clinical study in which the leukocyte oxidative output of whole blood was measured in three groups of patients. Two chemilumine scence markers (luminol or lucigenin), indicative of either total oxid ant output or superoxide production, and three stimuli (opsonized zymo san, formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate a cetate) (PMA), representing different pathways of leukocyte activation , were used. Tumor necrosis factor, interleukin-6 and C-reactive prote in (TNF, IL-6, and CRP) were determined to evaluate the severity of th e inflammatory process. Setting: Intensive care and surgical units of a university hospital. Patients: Seventy-four healthy patients, ten IC U patients without signs of sepsis or systemic inflammatory response s yndrome and 19 septic patients were studied. Measurement and main resu lts: With all three stimuli, whole blood total oxidative output and su peroxide production were generally increased in septic patients. This was most likely due to the increased leukocyte numbers in these patien ts. When the chemiluminescence values were normalized per phagocyte (g ranulocytes and monocytes), the total oxidative output of septic phago cytes decreased with opsonin and fMLP but increased with PMA, while su peroxide output decreased regardless of the stimuli used. TNF, IL-6 an d CRP, although increased in septic patients as compared to ICU contro ls, correlated weakly with oxidant output. Conclusions: The oxidative output of whole blood was increased in septic patients compared to con trols because of elevated leukocyte numbers. However, oxidant output n ormalized for phagocyte numbers generally decreases during sepsis for most stimuli. Cytokines and CRP do not appear to be associated with th e extent of oxidant output during sepsis.