Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and their role in multiple organ dysfunction

Clin Immunol. 2005 Aug;116(2):158-65. doi: 10.1016/j.clim.2005.03.006.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antithrombin III
  • Apoptosis / immunology
  • Cytokines / blood
  • Fibrinolysin / analysis
  • Granzymes
  • Humans
  • Interleukin-12 / blood
  • Interleukin-12 Subunit p40
  • Interleukin-6 / blood
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology*
  • Middle Aged
  • Multiple Organ Failure / blood*
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / immunology
  • Nucleosomes / metabolism
  • Peptide Hydrolases / blood
  • Plasminogen Activator Inhibitor 1 / blood
  • Protein Subunits / blood
  • Sepsis / blood*
  • Sepsis / immunology
  • Sepsis / mortality
  • Serine Endopeptidases / blood
  • Shock, Septic / blood*
  • Shock, Septic / complications
  • Shock, Septic / immunology
  • Statistics, Nonparametric
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • alpha-2-Antiplasmin / analysis
  • fas Receptor / blood

Substances

  • Cytokines
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • Nucleosomes
  • Plasminogen Activator Inhibitor 1
  • Protein Subunits
  • alpha-2-Antiplasmin
  • antithrombin III-protease complex
  • fas Receptor
  • plasmin-plasmin inhibitor complex
  • Interleukin-12
  • Antithrombin III
  • Peptide Hydrolases
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • Fibrinolysin
  • GZMA protein, human