Modulation of monocytes in septic patients: preserved phagocytic activity, increased ROS and NO generation, and decreased production of inflammatory cytokines

被引:46
作者
Santos S.S. [1 ]
Carmo A.M. [1 ]
Brunialti M.K.C. [1 ]
Machado F.R. [1 ]
Azevedo L.C. [2 ]
Assunção M. [3 ]
Trevelin S.C. [4 ]
Cunha F.Q. [4 ]
Salomao R. [1 ]
机构
[1] Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, Sao Paulo
[2] Hospital Sírio Libanes, Universidade de Sao Paulo, Ribeirao Preto
[3] Hospital Israelita Albert Einstein, Universidade de Sao Paulo, Ribeirao Preto
[4] Faculdade de Medicina, Universidade de Sao Paulo, Ribeirao Preto
关键词
IL-6; Monocytes; Nitric oxide; Phagocytosis; Reactive oxygen species; TNF-α;
D O I
10.1186/s40635-016-0078-1
中图分类号
学科分类号
摘要
Background: The nature of the inflammatory response underscoring the pathophysiology of sepsis has been extensively studied. We hypothesized that different cell functions would be differentially regulated in a patient with sepsis. We evaluated the modulation of monocyte functions during sepsis by simultaneously assessing their phagocytic activity, the generation of reactive oxygen species (ROS) and nitric oxide (NO), and the production of inflammatory cytokines (IL-6 and TNF-α). Methods: Whole blood was obtained from patients with severe sepsis and septic shock both at admission (D0, n = 34) and after seven days of therapy (D7, n = 15); 19 healthy volunteers were included as a control group. The cells were stimulated with LPS, Pseudomonas aeruginosa, and Staphylococcus aureus. The ROS and NO levels were quantified in monocytes in whole blood by measuring the oxidation of 2,7-dichlorofluorescein diacetate and 4-amino-5-methylamino-2,7-difluorofluorescein diacetate, respectively. Intracellular IL-6 and TNF-α were detected using fluorochrome-conjugated specific antibodies. Monocyte functions were also evaluated in CD163+ and CD163− monocyte subsets. Results: The monocytes from septic patients presented with preserved phagocytosis, enhanced ROS and NO generation, and decreased production of inflammatory cytokines compared with the monocytes from healthy volunteers. TNF-α and IL-6 increased and ROS generation decreased in D7 compared with D0 samples. In general, CD163+ monocytes produced higher amounts of IL-6 and TNF-α and lower amounts of ROS and NO than did CD163− monocytes. Conclusions: We demonstrated that monocytes from septic patients, which are impaired to produce inflammatory cytokines, display potent phagocytic activity and increased ROS and NO generation. © 2016, Santos et al.
引用
收藏
页码:1 / 16
页数:15
相关论文
共 31 条
[1]  
Bone R.C., Balk R.A., Cerra F.B., Dellinger R.P., Fein A.M., Knaus W.A., Schein R.M., Sibbald W.J., Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine, Chest, 101, pp. 1644-1655, (1992)
[2]  
Vincent J.L., Opal S.M., Marshall J.C., Tracey K.J., Sepsis definitions: time for change, Lancet, 381, pp. 774-775, (2013)
[3]  
Xiao W., Mindrinos M.N., Seok J., Cuschieri J., Cuenca A.G., Gao H., Hayden D.L., Hennessy L., Moore E.E., Minei J.P., Bankey P.E., Johnson J.L., Sperry J., Nathens A.B., Billiar T.R., West M.A., Brownstein B.H., Mason P.H., Baker H.V., Finnerty C.C., Jeschke M.G., Lopez M.C., Klein M.B., Gamelli R.L., Gibran N.S., Arnoldo B., Xu W., Zhang Y., Calvano S.E., McDonald-Smith G.P., Schoenfeld D.A., Storey J.D., Cobb J.P., Warren H.S., Moldawer L.L., Herndon D.N., Lowry S.F., Maier R.V., Davis R.W.,
[4]  
Hotchkiss R.S., Monneret G., Payen D., Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach, Lancet Infect Dis, 13, pp. 260-268, (2013)
[5]  
Riedemann N.C., Guo R.F., Ward P.A., Novel strategies for the treatment of sepsis, Nat Med, 9, pp. 517-524, (2003)
[6]  
Brown K.A., Brain S.D., Pearson J.D., Edgeworth J.D., Lewis S.M., Treacher D.F., Neutrophils in development of multiple organ failure in sepsis, Lancet, 368, pp. 157-169, (2006)
[7]  
Brunialti M.K., Martins P.S., Barbosa de Carvalho H., Machado F.R., Barbosa L.M., Salomao R., TLR2, TLR4, CD14, CD11B, and CD11C expressions on monocytes surface and cytokine production in patients with sepsis, severe sepsis, and septic shock, Shock, 25, pp. 351-357, (2006)
[8]  
Rigato O., Salomao R., Impaired production of interferon-gamma and tumor necrosis factor-alpha but not of interleukin 10 in whole blood of patients with sepsis, Shock, 19, pp. 113-116, (2003)
[9]  
Salomao R., Brunialti M.K., Kallas E.G., Martins P.S., Rigato O., Freudenberg M., Lipopolysaccharide-cell interaction and induced cellular activation in whole blood of septic patients, J Endotoxin Res, 8, pp. 371-379, (2002)
[10]  
Martins P.S., Brunialti M.K., Martos L.S., Machado F.R., Assuncao M.S., Blecher S., Salomao R., Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis, Crit Care, 12, (2008)