High interleukin 12 and low interleukin 10 production after in vitro stimulation detected in sepsis survivors

Objective: To evaluate viability of isolated peripheral blood mononuclear cells (PBMC) and production of cytokines in vitro after stimulation as prognostic factors for survival in sepsis patients. Design: Prospective study of the biological response of PBMC in the onset of severe sepsis. Setting: Research laboratory of molecular biology and immunology and university hospital ICU, Faculty of Medicine, Trakia University. Patients: Twenty-three patients meeting the criteria for severe sepsis, and 14 control subjects. Interventions: Isolated PBMC were stimulated in vitro with: C3-binding glycoprotein (C3bgp; 30 mug), lipopolysaccharide (30 mug), phytohemagglutinin (20 mug), pokeweed mitogen (30 mug), and dexamethasone (500 mug). Measurements and results: We measured the levels of interleukins (IL) 6, 10, and 12 in culture supernatants. Stimulation with C3bgp and phytohemagglutinin led to significantly lower PBMC secretion of IL-6 in nonsurvivors than in survivors and healthy donors. Stimulation with C3bgp, lipopolysaccharide, and pokeweed mitogen considerably reduced IL-12 production in nonsurvivors. Stimulation with lipopolysaccharide and pokeweed mitogen caused immune cells in nonsurvivors to produce higher levels of IL-10 than in survivors. Survival of PBMC reduced viability for nonsurvivors' PBMC, both spontaneously and as induced by lipopolysaccharide or pokeweed mitogen. Conclusions: The viability of PBMC at the onset of sepsis and enhanced production of IL-12 and diminished production of IL-10 after stimulation with all stimuli used may be a favorable prognostic factor in sepsis.