Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early infection and suggest novel diagnostic and therapeutic approaches.

Both SOFA and RIFLE category showed high discriminative power in predicting hospital mortality in critically ill patients with cirrhosis. The RIFLE classification is a simple and easily applied evaluative tool with good prognostic abilities.

Background. End-stage liver disease is often complicated by renal function disturbances. Cirrhotic patients with acute renal failure admitted to intensive care units (ICUs) have high mortality rates. This work seeks to identify specific predictors of hospital mortality in critically ill cirrhotic patients with acute renal failure. Methods. A total of 111 patients with cirrhosis and acute renal failure were admitted to ICU from March 2003 to February 2005. Twenty-six demographic, clinical and laboratory variables were prospectively gathered as predictors of survival on the first day of ICU admission. Results. The overall hospital mortality rate was 81.1%. The univariate analysis identified 11 of the 32 variables as prognostically valuable. The multiple logistic regression analysis (excluding five scoring systems) indicates that the mean arterial pressure (MAP), serum bilirubin, respiratory failure and sepsis on the first day in ICU are significantly related to prognosis. The best Youden index (sensitivity + specificity − 1) yields cutoff points of 80 MAP (in mmHg) and 80 serum bilirubin (in µmol/L) (or 4.7 mg/dL) and indicates acute respiratory failure and sepsis. A simple model for mortality is developed on the basis of these four readily available parameters on Day 1 of ICU admission. The new score (MBRS score: MAP + bilirubin + respiratory failure + sepsis) displays an excellent area under the receiver operating characteristic curve (0.898 ± 0.031, P < 0.001). The mortality rate exceeds 90% when the MBRS (MAP + bilirubin + respiratory failure + sepsis) score is 2 or higher. Conclusion. The MBRS score is a straightforward, reproducible and easily adopted evaluative tool with good prognostic abilities, which generates objective data for patient families and physicians and supplements a clinical judgment of prognosis.