Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome

LC Casey, RA Balk, RC Bone - Annals of internal medicine, 1993 - acpjournals.org
LC Casey, RA Balk, RC Bone
Annals of internal medicine, 1993acpjournals.org
Objective: To determine whether plasma tumor necrosis factor-(TNF-), interleukin-1 (IL-1),
interleukin-6 (IL-6), and lipopolysaccharide are detectable in patients when they first present
with the sepsis syndrome and to determine whether levels correlate with patient survival.
Design: Prospective study comparing patients with the sepsis syndrome, critically ill patients
without sepsis, and normal healthy volunteers. Setting: Tertiary care hospital affiliated with a
medical school. Patients: The study included 97 consecutive patients on a medical service …
Objective
To determine whether plasma tumor necrosis factor- (TNF-), interleukin-1 (IL-1 ), interleukin-6 (IL-6), and lipopolysaccharide are detectable in patients when they first present with the sepsis syndrome and to determine whether levels correlate with patient survival.
Design
Prospective study comparing patients with the sepsis syndrome, critically ill patients without sepsis, and normal healthy volunteers.
Setting
Tertiary care hospital affiliated with a medical school.
Patients
The study included 97 consecutive patients on a medical service who met the criteria for the sepsis syndrome; 20 critically ill patients without sepsis who were in the medical intensive care unit; and 20 healthy volunteers who served as comparison groups.
Measurements
Plasma tumor necrosis factor-, IL-1 , interleukin-6, and endotoxin (lipopolysaccharide) levels were measured when a patient was first identified as having the sepsis syndrome. Survival was defined as being alive 30 days after the sepsis syndrome was diagnosed.
Results
Fifty-four percent of patients with the sepsis syndrome had detectable levels of TNF- (median, 26 pg/mL; range, nondetectable to 1000 pg/mL); 37% had detectable levels of IL-1 (median, 20 pg/mL; range, nondetectable to 2850 pg/mL); 80% had detectable levels of IL-6 (median, 415 pg/mL; range, nondetectable to 2380 pg/mL); and 89% had detectable levels of lipopolysaccharide (median, 2.6; range, nondetectable to 12.5 endotoxin units [EU]/mL). In all cases, levels were higher than those in critically ill patients without sepsis and normal healthy controls (P < 0.001 for all comparisons). Plasma levels of TNF-, IL-1 , IL-6, and lipopolysaccharide were detectable in patients regardless of culture status. The IL-6 level was 69% (95% CI, 30% to 108%) higher in patients who died compared with those who survived. The scores for the individual levels of TNF-, IL-1 , IL-6, and lipopolysaccharide were summed to arrive at a total lipopolysaccharide-cytokine score, and mortality increased with lipopolysaccharide-cytokine score (P < 0.001).
Conclusions
Patients with the sepsis syndrome have detectable levels of circulating TNF-, IL-1, IL-6, and lipopolysaccharide independent of culture-documented infection. Lipopolysaccharide and cytokines may play a pathogenic role in sepsis, and the combination of several elevated factors may be important in determining patient survival.
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