Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and their role in multiple organ dysfunction.
To evaluate the role of activated cytotoxic cells in patients with severe sepsis (n = 32) or septic shock (n = 8), direct (granzymes A and B) as well as indirect markers (cytokines) for cytotoxic cell activation were measured. Elevated IL-12p40 levels had been detected in 58% of the sepsis patients, whereas only a few had detectable TNF-alpha, IFN-gamma, or IL-12p70 levels. Granzymes A and B levels were elevated in 42.5% and 22.5%, respectively. IL-12p40 inversely correlated with disease severity. Inflammatory parameters (IL-6) and coagulation markers were significantly lower and higher, respectively, in patients with elevated IL-12p40 and granzyme B levels, as compared to those with normal levels. Elevation of granzyme A directly correlated with the increase of apoptotic markers. Activated cytotoxic cells reflected by elevated granzymes A and/or B were found in 50% of our sepsis patients. This group showed a higher mortality and a worse organ function.
Central Hematology Laboratory, Inselspital, Bern, Switzerland.
Sacha
S
Zeerleder
C Erik
CE
Hack
Christoph
C
Caliezi
Gerard
G
van Mierlo
Anke
A
Eerenberg-Belmer
Angela
A
Wolbink
Walter A
WA
Wuillenmin
D000328:Adult; D000368:Aged; D000990:Antithrombin III; D017209:Apoptosis / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005341:Fibrinolysin / Q000032:analysis; D053804:Granzymes; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology / Q000276:immunology; D009707:Nucleosomes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D021122:Protein Subunits / Q000097:blood; D018805:Sepsis / Q000097:blood* / Q000276:immunology / Q000401:mortality; D012697:Serine Endopeptidases / Q000097:blood; D012772:Shock, Septic / Q000097:blood* / Q000150:complications / Q000276:immunology; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000032:analysis; D019014:fas Receptor / Q000097:blood
D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D009707:Nucleosomes; D017395:Plasminogen Activator Inhibitor 1; D021122:Protein Subunits; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; D019014:fas Receptor; C037742:plasmin-plasmin inhibitor complex; D018664:Interleukin-12; D000990:Antithrombin III; D010447:Peptide Hydrolases; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D005341:Fibrinolysin; C509212:GZMA protein, human