Soluble granzymes are released during human endotoxemia and in patients with severe infection due to gram-negative

F N Lauw1, A J Simpson, C E Hack

  • 1Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. fnlauw@hotmail.com

Insights

Granzyme A (GrA) and Granzyme B (GrB) levels increase during bacterial infections, indicating immune cell involvement. Cytokine neutralization affects granzyme release, suggesting a role in bacterial immune responses.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Extracellular granzyme release signifies cytotoxic T lymphocyte and NK cell activity in disease.
  • Understanding granzyme dynamics during bacterial infections is crucial for immune response insights.

Purpose of the Study:

  • To investigate granzyme release patterns during bacterial infections.
  • To explore the role of cytokines in granzyme secretion during bacterial challenges.

Main Methods:

  • Measured plasma granzyme A (GrA) and GrB levels in experimental human endotoxemia and melioidosis patients.
  • Stimulated whole blood with bacteria and assessed granzyme secretion following cytokine neutralization.

Main Results:

  • Transient GrA and GrB increases observed post-endotoxin, peaking at 2-6 hours.
  • Elevated GrA and GrB levels persisted in patients with bacteremic melioidosis.
  • Cytokine neutralization (TNF, IL-12, IL-18) inhibited granzyme secretion, independent of interferon-gamma.
  • Bacterial stimulation induced significant granzyme secretion, indicating a general immune response.

Conclusions:

  • Granzyme release is a general immune response to bacterial infections.
  • Cytokine networks interact with granzymes, potentially playing an immunoregulatory role.

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