ABSTRACT
BACKGROUND AND OBJECTIVE: Sepsis is a leading cause of acute lung injury (ALI); however, the characteristics and outcome of sepsis-associated ALI are poorly understood. We aimed to elucidate factors that predict patient outcome in sepsis-associated ALI. METHODS: Secondary analysis of a multicenter, prospective, observational study was performed. RESULTS: Among 624 patients with severe sepsis and septic shock, 251 (40.2%) fulfilled the definition of American-European Consensus Conference definition of ALI. All-cause 28-day and in-hospital mortalities were 30.7% and 38.6%, respectively. More than 40% of ALI patients had neurological, cardiovascular and haematological dysfunctions or disseminated intravascular coagulation, all of which were associated with higher mortality. We report a significant correlation between infection site and mortality in patients with ALI, but not in those without ALI. The proportion of ALI was significantly higher in pulmonary sepsis; further, a complication of ALI was associated with higher mortality in sepsis from pulmonary and other sources, but not in abdominal sepsis. Among the other sepsis sites, urinary tract, central nervous system, catheter-related and undetermined foci of infection had worse outcomes when associated with ALI. None of the individual severe sepsis bundles, including fluid resuscitation and early antibiotic administration, correlated with mortality. Compliance with a set of sepsis management bundles was associated with better outcomes. CONCLUSION: In severe sepsis and septic shock, the proportion and effect on outcome was not uniform among infection sites. The infection site was predictive of outcome in patients with ALI but not in those without ALI.
Subject(s)
Acute Lung Injury , Focal Infection , Lung Diseases , Sepsis , Shock, Septic , Acute Lung Injury/diagnosis , Acute Lung Injury/etiology , Acute Lung Injury/mortality , Causality , Disease Management , Female , Focal Infection/complications , Focal Infection/diagnosis , Hospital Mortality , Humans , Japan/epidemiology , Lung Diseases/complications , Lung Diseases/diagnosis , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Outcome and Process Assessment, Health Care , Prognosis , Prospective Studies , Sepsis/complications , Sepsis/epidemiology , Sepsis/therapy , Shock, Septic/complications , Shock, Septic/epidemiology , Shock, Septic/therapyABSTRACT
Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRII(bright) suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRII(bright) cells from these mice. The increase of FcγRII(bright) cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRII(bright) cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRII(bright) suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRII(bright) suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.
ABSTRACT
Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRIIbright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRIIbright cells from these mice. The increase of FcγRIIbright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRIIbright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRIIbright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRIIbright suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.
