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To determine the role of CD14 in lipopolysaccharide (LPS)-induced effects on coagulation and fibrinolysis in humans, 16 healthy subjects received an intravenous injection of LPS preceded by intravenous IC14, a recombinant chimeric monoclonal antibody against human CD14, or placebo. LPS-induced coagulation activation (tissue-factor mRNA in whole blood cells and plasma concentrations of F1+2) was not influenced by IC14, whereas the antibody reduced the increase in thrombin-antithrombin complexes and soluble fibrin. LPS injection also was associated with an early activation of fibrinolysis (plasma concentrations of tissue-type plasminogen activator and plasmin-alpha(2)-antiplasmin complexes), followed by an inhibitory response (plasminogen activator inhibitor type 1), which were attenuated by IC14. Furthermore, LPS reduced thrombin-activatable fibrinolysis-inhibitor antigen levels and increased soluble thrombomodulin levels, which were not influenced by IC14. These results suggest that different hemostatic responses during endotoxemia may proceed via CD14-dependent and -independent pathways.

mice. In contrast, mice treated with anti–I FN-g did not demonstrate a consistently altered bacterial outgrowth, compared with mice treated with a control antibody. These data suggest that endogenous IFN-g, despite its protective role in defense against intracellular pathogens, does not serve a protective role during pneumococcal pneumonia. Streptococcus pneumoniae is a gram-positive bacterium responsible for .50% of the cases of community-acquired pneumonia. Pneumococcal pneumonia is the fifth leading cause of death worldwide, and, among patients with communityacquired pneumonia who require hospitalization, the mortality rate is as high as 25% [1, 2]. Against this background, and because of the growing resistance of the pneumococcus to antimicrobial therapy, it is important to gain insight into the pathogenesis of pneumococcal pneumonia [3]. Innate defense mechanisms play an important role in the elimination of bacteria from the alveolus. Phagocytic cells, as well as residential NK cells and T cells, participate in this response via the elaboration of chemotactic and regulatory cytokines [4]. Interferon (IFN)‐g is a potent proinflammatory cytokine, produced mainly by antigen-activated T and NK cells. IFN-g exerts several immune regulatory activities, including activation of phagocytes, stimulation of antigen presentation by increasing the expression of class I and II major histocompatibility complex molecules on antigen-presenting cells, orchestration of leukocyteendothelium interactions, and stimulation of the respiratory

CXC chemokines have been implicated in the recruitment of neutrophils to sites of infection. To determine the role of CXC chemokines in the host response to urinary tract infection (UTI), female mice were treated with an antibody against the major CXC chemokine receptor in the mouse, CXCR2, before intravesical inoculation with Escherichia coli. Anti-CXCR2 prevented the influx of neutrophils in urine and kidneys. The absence of a neutrophil response only temporarily impaired the clearance of bacteria from the urinary tract, as indicated by 100- and 1000-fold more E. coli colony-forming units in urine and kidneys of anti-CXCR2-treated mice at 24 h, but not at 48 h, after the infection. UTI induced increases in the renal concentrations of the CXCR2 ligands macrophage inflammatory protein-2 and KC, which were not influenced by anti-CXCR2 administration. CXC chemokines play an important role in the development of a local inflammatory response to UTI.

CXC chemokines are chemotactic cytokines that specifically act on neutrophils. To obtain insight into the extent of local production of CXC chemokines during acute pyelonephritis, interleukin (IL)-8, growth-related oncogene (GRO)-alpha, and epithelial cell-derived neutrophil-activating protein (ENA)-78 were measured in urine and plasma samples from patients with culture-proven urosepsis (n=33), healthy human control subjects with sterile urine (n=31), and human volunteers intravenously injected with endotoxin (n=11). Patients had profoundly elevated urine concentrations of chemokines with no (GRO-alpha and ENA-78) or little (IL-8) elevation in plasma. Endotoxin-challenged subjects demonstrated transient increases in plasma chemokine concentrations, with no (GRO-alpha) or little (IL-8 and ENA-78) elevation in urine. Urine from patients exerted chemotactic activity toward neutrophils, which was partially inhibited by neutralizing antibodies against IL-8, GRO-alpha, or ENA-78. During urosepsis, CXC chemokines are predominantly produced within the urinary tract, where they are involved in the recruitment of neutrophils to the urinary compartment.