Reduced tumor necrosis factor alpha production in lipopolysaccharide-treated whole blood from patients in the intensive care unit
J. C. Setrakian, J. Yee and N. V. Christou
Department of Surgery, McGill University, Montreal, Quebec.
OBJECTIVE: To determine the cytokine response to lipopolysaccharide in
patients in the intensive care unit. PATIENTS: Patients in a mixed
medical/surgical intensive care unit with fever and a de novo clinical
dysfunction of at least one organ system. METHODS: Whole blood from
patients and from laboratory controls was stimulated with 8 ng/mL of
lipopolysaccharide (Escherichia coli 0111:B4) at 37 degrees C, and tumor
necrosis factor alpha (TNF-alpha) was measured using enzyme linked
immunosorbent assay at 4, 8, and 24 hours. The same subjects' purified
monocytes were cultured with 8 ng/mL of lipopolysaccharide in the presence
of autologous or pooled control plasma or cocultured with purified
autologous polymorphonuclear leukocytes at a polymorphonuclear
leukocyte-monocyte ratio of 10:1, and TNF-alpha was measured at 24 hours
using the enzyme linked immunosorbent assay. RESULTS: We detected high (n =
5) and low (n = 5) TNF-alpha responders in whole blood producing a mean
(+/- SEM) of 27.2 +/- 6.3 pg/mL per 1000 monocytes vs 0.0 +/- 2.4 pg/mL per
1000 monocytes, respectively (controls, 58.0 +/- 13.0 pg/mL per 1000
monocytes). The kinetics of TNF-alpha production in both groups were
comparable. Purified monocytes from both groups of patients cultured with
lipopolysaccharide alone produced equivalent TNF-alpha values (42.4 +/-
10.5 vs 40.8 +/- 12.5 pg/mL per 1000 monocytes). Assayable TNF-alpha was
not different with autologous vs control serum but was markedly diminished
by the presence of polymorphonuclear leukocytes in patients as well as in
controls; the two groups of patients did not differ in this
polymorphonuclear leukocyte effect. CONCLUSION: Lipopolysaccharide
stimulation of monocytes in the whole blood results in marked variation of
TNF-alpha production. This phenomenon may account for the variable septic
response to infection in patients in the intensive care unit.
