Impaired production of interferon-gamma and tumor necrosis factor-alpha but not of interleukin 10 in whole blood of patients with sepsis.
It has been demonstrated that lipopolysaccharide (LPS)-induced cytokine response in patients with sepsis differ from the normal host, yet this has not been controlled for the presence of underlying disease. We studied the ability of LPS and killed gram-negative bacteria (GNB) to induce tumor necrosis factor (TNF)-alpha and interleukin (IL) 10, and of phytohemagglutinin (PHA) to induce interferon (IFN)-gamma, in whole blood from patients with sepsis (SP, n = 20), patients with matched underlying disease and without sepsis (control patients, n = 20), and healthy volunteers (HV, n = 20). LPS-induced TNF-alpha production was lower in SP (median = 638 pg/mL) compared with control patients (4060 pg/mL; P= 0.003), and control patients production was lower compared with HV (5329 pg/mL; P < 0.001). Pseudomonas aeruginosa-induced TNF-alpha production was lower in SP (1443 pg/mL) than in control patients (7319 pg/mL; P < 0.05), and was not different between control patients and HV (6612 pg/mL; P = 0.6). IFNy production was lower in SP (948 pg/mL) compared with control patients (5516 pg/mL; P < 0.001), and the control patients production was lower compared with HV (11,282 pg/mL; P < 0.001). IL-10 production was not different among the three groups. Down-regulation of TNF-alpha production in patients with sepsis, although not restricted to them, was more pronounced with LPS than with GNB. Although the presence of underlying disease may be involved in the regulatory mechanisms of host response, the use of controls with matched underlying diseases provides strong evidence for the septic condition in the down-regulation of inflammatory response in patients with sepsis.
Rigato
Otelo
O
Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, Universiolade Federal de São Paulo, CEP 04039-032, São Paulo, SP, Brazil.
Salomao
Reinaldo
R
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000097:blood* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma