Abstract
The establishment of a local inflammatory response with production of cytokines/chemokines and the consequent neutrophil recruitment are critical to control an infection. In this context, our group had demonstrated an impairment of neutrophil migration toward the infectious focus in severe sepsis. The failure of neutro-phil migration is markedly associated with increased systemic cytokines levels and high mortality of the severe sepsis, either in experimental models or in patients. Recently, the participation of Toll-like receptors (TLRs) in the failure of neutrophil migration was described. Caspase-1 seems to be important in the activation of TLR signaling pathways. Moreover, it is also critical to the activation of inflammatory cytokines IL-1β, IL-18 and IL-33. The aim of the present study was to evaluate the participation of caspase-1 during severe sepsis. The caspase-1-deficient mice presented increased resistance to severe sepsis induced by CLP. However, IL-18 and ST2 (receptor of IL-33)-deficient mice did not present a reduction of mortality after sepsis. The treatment with antagonist of IL-1 receptor was also unable to modify the survival rate of wild-type mice that underwent severe sepsis. These data indicate that the reduction in levels of these cytokines is not critical for reduction of mortality observed in caspase-1-deficient mice. The reduction in mortality of caspase-1-deficient mice was associated with decreased systemic levels of TNFα and IL-6. Despite the unaltered local levels of cytokines and chemokines, caspase-1-deficient mice that underwent severe sepsis presented a marked increase in neutrophil migration to the peritoneal cavity, which was supported by an increased rolling and adhesion of leukocytes in these mice. As consequence, a reduced bacterial growth in peritoneal exudates and blood was observed in these animals, although neutrophils from caspase-1-deficient and wild-type mice presented similar killing and cellular viability. Thus, in the absence of caspase-1, neutrophil migration to the peritoneal cavity is increased and culminates in a reduction of mortality because of efficient control of the infection.
Highlights
Many authors have written about the need to treat patients closer to their beds, in order to observe them more as distinct people
We found that CCR2–/– mice subjected to severe sepsis by cecal ligation and puncture (CLP) exhibited reduced neutrophil infiltration in the heart, lung and kidney and an enhanced survival rate when compared with WT mice subjected to severe sepsis
Our findings demonstrated that Toll-like receptors (TLRs) activation induced the CCR2 expression and CCL2 responsiveness in human and murine neutrophils, and this expression profile in neutrophils is involved in the detrimental infiltration of these cells in distant tissues during server sepsis
Summary
Many authors have written about the need to treat patients closer to their beds, in order to observe them more as distinct people. Aortic dissection and aneurysm groups were analyzed against each other; and AAD patients were compared with paired matched CABG brackets for morbidity (postoperative complications and ICU and hospital lengths of stay) and 1-month and 6-month mortality. The incidence of VAP is high, varying between 6% and 52%, depending on the studied population, on the type of UTI and on the type of diagnosis technique used; in spite of being an extremely important infection, it is one of the most difficult diagnoses in critically ill patients. The objective of the present study was to assess the effectiveness of a daily MDR to improve compliance with the VAP bundle recommendations and other beneficial prophylactic measures in a high-volume critical care unit. Objective To verify the validity of the ADHERE CART method to stratify the risk of inhospital mortality of patients admitted with ADHF in a high-complexity Brazilian hospital
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