Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

Introduction Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. Methods Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNF alpha) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNF alpha, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. Results Mortality rates of patients with apoptosis <= 50% compared with patients with apoptosis > 50% were 49.12% and 15.15%, respectively ( P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis > 50% compared with those patients with apoptosis <= 50% ( P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis <= 50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNF alpha were higher in patients with monocyte apoptosis <= 50% and septic shock compared with patients with apoptosis > 50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. Conclusion Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis.