Soluble Granzymes Are Released during Human Endotoxemia and in Patients with Severe Infection Due to Gram-Negative Bacteria

Extracellular release of granzymes is considered to reflect the involvement of cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight into granzyme release during bacterial infection, granzyme levels were measured during experimental human endotoxemia and in patients with...

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Bibliographic Details
Published in:The Journal of infectious diseases 2000-07, Vol.182 (1), p.206-213
Main Authors: Lauw, Fanny N., Simpson, Andrew J. H., Erik Hack, C., Prins, Jan M., Wolbink, Angela M., van Deventer, Sander J. H., Chaowagul, Wipada, White, Nicholas J., van der Poll, Tom
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Bacterial diseases
Biological and medical sciences
Blood
Blood plasma
Burkholderia pseudomallei
Cytokines
Cytokines - metabolism
Endotoxemia
Endotoxemia - enzymology
Endotoxemia - immunology
Endotoxemia - metabolism
Female
Follow-Up Studies
Gram-Negative Bacterial Infections - enzymology
Gram-Negative Bacterial Infections - immunology
Gram-Negative Bacterial Infections - metabolism
granzyme A
granzyme B
Granzymes
Health care administration
Human bacterial diseases
Humans
Infections
Infectious diseases
Lipopolysaccharides - pharmacology
Lymphocyte Activation
Lymphocyte Count - drug effects
Lymphocytes
Major Articles
Male
Medical sciences
Melioidosis
Melioidosis - immunology
Melioidosis - pathology
Middle Aged
Natural killer cells
Secretion
Serine Endopeptidases - metabolism
T-Lymphocytes, Cytotoxic - physiology
Time Factors
Tropical bacterial diseases
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Summary:Extracellular release of granzymes is considered to reflect the involvement of cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight into granzyme release during bacterial infection, granzyme levels were measured during experimental human endotoxemia and in patients with melioidosis, a severe infection due to gram-negative bacteria. Plasma concentrations of granzyme A (GrA) and GrB increased transiently after endotoxin administration, peaking after 2–6 h. In patients with bacteremic melioidosis, GrA and GrB levels were elevated on admission and remained high during the 72-h study period. In whole blood stimulated with heat-killed Burkholderia pseudomallei, neutralization of tumor necrosis factor, interleukin-12, or interleukin-18 inhibited granzyme secretion, which was independent of interferon-γ. Stimulation with endotoxin and other gram-negative and gram-positive bacteria also strongly induced the secretion of granzymes, suggesting that granzyme release is a general immune response during bacterial infection. The interaction between the cytokine network and granzymes may play an important immunoregulatory role during bacterial infections.
ISSN:0022-1899
1537-6613
DOI:10.1086/315642