Evaluation of endotoxin release and cytokine production induced by antibiotics in patients with Gram-negative nosocomial pneumonia

Objective: To determine the plasma concentrations of lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in a homogeneous group of septic patients and to evaluate the effect of antibiotic treatment, imipenem or ceftazidime, on the release of lipopolysaccharide and cytokines. Design: Prospective, randomized study. Setting: Sixteen-bed multidisciplinary intensive care unit. Patients: Twenty-four septic patients with documented Gram-negative nosocomial pneumonia. Controls were 20 patients admitted without sepsis and 20 healthy volunteers. Interventions: Septic patients were randomized between imipenem and ceftazidime. Blood samples were collected before (0 hrs) and after (4 and 12 hrs) antibiotic treatment. Concentrations of lipopolysaccharide were measured by using the limulus assay, and cytokine concentrations were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed by Kruskal-Wallis test, Mann-Whitney U test, and Student's t-test. Measurements and Main Results: The mean age was 48.5 19.5. The mean Acute Physiology and Chronic Health Evaluation 11 score was 18.4 +/- 4.5. Overall mortality rate was 45.4%. All septic patients showed significant higher concentrations of lipopolysaccharide (p <.001), tumor necrosis factor-alpha (p <.04), and interleukin-6 (p <.001) than the controls, but interleukin-1beta was never detected. We did not find statistically significant changes in lipopolysaccharide or cytokine plasma concentrations over time within any of the two arms of the study (ceftazidime vs. imipenem). There were no statistically significant differences in lipopolysaccharide and interleukin-6 plasma concentrations between the two antibiotic treatments. Although tumor necrosis factor-a plasma concentrations were significantly higher in the group treated with ceftazidime compared with the group treated with imipenem at the baseline and 4 hrs later, these differences were not statistically significant after 12 hrs of initiation of both treatments. Conclusions. Patients with Gram-negative nosocomial pneumonia have high plasma concentrations of lipopolysaccharide, interleukin-6, and tumor necrosis factor-a, but the antibiotic therapy evaluated did not significantly modify these concentrations.