Death In Septic Patients Research Articles

Susceptibility to programmed cell death in T-lymphocytes from septic patients: a mechanism for lymphopenia and Th2 predominance

Sepsis causes lymphopenia which is inversely correlated with patient survival. The role of apoptosis-specific immune-activation and activation-induced cell-death in sepsis is incompletely understood. Fifteen septic patients and 20 healthy controls were included. T-cell proliferation was measured by [ 3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNFR1, sCD95, interleukin-1β converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T-cell proliferation were significantly decreased in septic patients. The percentages of CD3 + and CD4 + T cells and CD19 + B cells were significantly reduced. Percent memory T-cells (CD45RO +) and cells undergoing apoptosis (CD95 +/annexin-V +) were significantly increased in sepsis. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Anti-CD3 antibody triggering induced a 56% increase of CD4 T-cell death in septic patients vs. 7.5% in controls relative to IgG. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in septic patients Th1 T-cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.

Interleukin-12 and -18 induce severe liver injury in mice recovered from peritonitis after sublethal endotoxin challenge

Background. Postoperative intraabdominal abscess is the major complication after abdominal surgery, and additional infection is often observed and becomes the leading cause of death in septic patients who survive initial resuscitation. Sepsis is initiated and perpetuated by the overzealous systemic production of proinflammatory cytokines—such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-18—sometimes resulting in excessive tissue injury and death. The purpose of this study was to assess the correlation between liver and spleen innate cytokine responses and organ dysfunction in sepsis syndrome. Methods. Peritonitis was induced by cecal ligation and puncture (CLP). All CLP mice survived more than 7 days after the procedure, and serum cytokine (TNF-α, IL-12, IL-18, and IL-10) levels peaked 12 hours after CLP; thereafter, they returned to basal levels 7 days after CLP. The mice were injected with a sublethal dose of lipopolysaccharide (LPS) 7 days after CLP. Survival rates, tissue damage, serum cytokine levels, and cytokine production of liver or spleen mononuclear cells (MNCs) were evaluated. Results. All CLP mice died within 6 hours from liver injury 7 days after LPS challenge, but all sham mice survived. IL-12, IL-18, and IFN-γ levels in supernatants of the liver MNCs stimulated with LPS in CLP mice were significantly higher than those in sham mice 7 days after the procedure. Furthermore, serum IL-12 and IL-18 levels and liver MNCs IL-12, IL-18, and IFN-γ production were significantly increased in CLP mice compared with sham mice after LPS challenge. Thereafter, effects of anti-IL-12 and/or anti-IL-18 antibody were evaluated in LPS-injected CLP mice. The survival rate of LPS-injected CLP mice treated with both anti-IL-12 and anti-IL-18 antibody was significantly better than that of untreated mice. Furthermore, liver damage was improved. Conclusion. Mice recovered from mild peritonitis died of severe liver injury by subsequent injection of a sublethal dose of LPS, and this liver injury was related to the collaborating production of IL-12 and IL-18 by liver MNCs.(Surgery 2003;134:92-100.)

Time course of organ dysfunction comparing survivors and nonsurvivors: results of the multicentric study 'Sepsis occurrence in the acutely ill patients' (SOAP)

Multiple organ dysfunction syndrome (MODS) is the main reason for death in septic patients. Most scoring systems are aimed to calculate a sum parameter for estimating the individual risk of the patient. This analysis describes the time course of organ dysfunction comparing survivors and nonsurvivors.