CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial pneumonia

Objectives: In patients with septic shock, circulating monocytes become ref ractory to stimulation with microbial products. Whether this hyporesponsive e state is induced by infection or is related to shock is unknown. To addr ess this question, we measured TNF alpha production by monocytes or by whol e blood obtained from healthy volunteers (controls), from patients with sep tic shock, from patients with severe infection (bacterial pneumonia) withou t shock, and from patients with cardiogenic shock without infection. Measurements: The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flo w cytometry. Monocytes or whole blood were stimulated with lipopolysacchari de endotoxin (LPS), heat-killed Escherichia roll or Staphylococcus aureus, and TNF alpha production uas measured by bioassay: Results: The number of circulating monocytes, of CD14+ monocytes, and the m onocyte CD14 expression were significantly lon er in patients with septic s hock than in controls, in patients with bacterial pneumonia or in those wit h cardiogenic shock (p <0.001). Monocytes or whole blood of patients with s eptic shock exhibited a profound deficiency of TNFa production in response to all stimuli (p <0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p <0.05 compared to controls ), although to a lesser extent, despite normal monocyte counts and normal C D14 expression. Conclusion: Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF<alpha> production in response to a broad range of infectious stimuli. Thus, down-regulation of c ytokine production appears to occur in patients with systemic, but not loca lised, albeit severe, infections and also in patients with non-infectious c irculatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors a re at work in this group and in patients with cardiogenic shock.