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Subduing the Inflammatory Cytokine Storm.

Raymond Kaempfer1

  • 1Department of Biochemistry and Molecular Biology, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.

International Journal of Molecular Sciences
|October 26, 2024
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Summary

Researchers developed peptide mimetics targeting the B7/CD28 axis to control harmful cytokine storms. These peptides show promise in treating severe bacterial infections and preventing multi-organ damage.

Keywords:
B7CD28costimulatory receptorcytokine stormhomodimer interfaceimmune costimulationinflammatory cytokineslethal toxic shockmimetic peptides

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Area of Science:

  • Immunology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Exaggerated inflammatory cytokine responses, or cytokine storms, contribute to severe disease and lethality in various infections.
  • Bacterial sepsis and toxic shock, especially with multidrug-resistant strains, pose significant threats.
  • The B7/CD28 costimulatory axis plays a crucial role in regulating immune responses.

Purpose of the Study:

  • To develop a molecular tool to analyze the B7/CD28 axis in human inflammatory responses.
  • To create a therapeutic strategy to attenuate cytokine storms while preserving host defense.
  • To investigate the efficacy of peptide mimetics targeting CD28-B7 interactions.

Main Methods:

  • Designed short peptide mimetics mimicking human CD28 and B7 receptor homodimer interfaces.
  • Utilized these peptides as molecular tools to dissect the B7/CD28 costimulatory axis.
  • Tested peptide efficacy in mouse models of bacterial superantigen-induced toxic shock and in the context of necrotizing soft tissue infections.

Main Results:

  • Peptide mimetics effectively attenuated the inflammatory response.
  • Mice treated with peptides were protected from lethal Gram-positive bacterial superantigen-induced toxic shock.
  • Peptides demonstrated efficacy at molar amounts significantly lower than the inducing agent.

Conclusions:

  • Peptide mimetics targeting the CD28-B7 engagement offer a novel therapeutic strategy against cytokine storms.
  • This approach holds promise for treating severe bacterial infections like toxic shock and necrotizing soft tissue infections.
  • The developed peptides serve as valuable tools for understanding inflammatory mechanisms.