Apoptosis of peripheral blood mononuclear cells in patients with sepsis

<b>Context:</b> Recent investigations into the pathogenesis of sepsis reveal an important role for apoptosis. The present study was designed in order to assess the peripheral blood mononuclear cells&#x2032; (PBMCs) apoptosis and the plasma levels of molecules associated with apoptosis belonging to tumor necrosis factor-alpha (TNF-&#945;)/tumor necrosis factor type-1 receptor (TNFR I) pathway in patients with sepsis. <b>Patients and Methods:</b> Twenty-two patients with sepsis and 20 healthy subjects were included in the study. The percentage of PBMCs&#x2032; apoptosis was examined using annexin-V at the time of blood draws (0 time). PBMCs were incubated for 24 hour at 37&#176;C in medium (spontaneous apoptosis) and in the presence of TNF-&#945;. After incubation, the percentage of apoptotic cells was counted. Plasma levels of TNF-&#945; and soluble TNFR I (sTNFR I) were also measured by enzyme linked immunosorbent assay (ELISA). <b>Results:</b> PBMCs of patients showed a higher proportion of apoptotic cells than PBMCs of controls at 0 time. After 24 hour incubation, spontaneous apoptosis of PBMCs was nearly as high as that of TNF induced apoptosis. Compared with healthy volunteers, patients with sepsis had elevated levels of TNF-&#945; and sTNFR I. <b>Conclusions:</b> The data indicate that a higher fraction of PBMCs was undergoing apoptosis <i>in vivo</i> in patients than controls. Enhanced <i>in vitro</i> apoptosis has also been observed in patients with sepsis, suggesting that a greater number of mononuclear cells in the peripheral circulation of patients are preprogrammed <i>in vivo</i> to undergo apoptosis. The circulating levels of both TNF-&#945; and sTNFR I from patients were significantly higher (<i>P</i> &lt; 0.001) than controls. The increase in levels of TNF-&#945; is proportional to that of sTNFR I (<i>r</i> = 0.908), indicating that sTNFR I may have a protective effect in the early stage of sepsis.