Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Bacterial sepsis

Pepducins to the rescue

Nature Reviews Drug Discovery volume 4, pages 538–539 (2005)Cite this article

A crucial player in the pathogenesis of sepsis is the chemokine interleukin 8 (IL-8) — mice deficient for its receptor CXCR2 (a GPCR) are protected from developing sepsis. Kaneider et al. now report the development of pepducins based on the i3 and i1 intracellular loops of CXCR2 and CXCR1 (a second IL-8 receptor in humans) that proved to be extremely powerful in inhibiting IL-8 signalling: in human neutrophils, these compounds completely inhibited IL-8-induced calcium responses and migration towards IL-8 chemotactic gradients.

Using the caecal ligation and puncture (CLP) mouse model of lethal sepsis, the authors demonstrated that the survival rate of mice injected subcutaneously with these pepducins was dramatically enhanced: whereas 17/17 untreated mice died of sepsis, only one of 34 died in the group that received once-daily injections. Even when this treatment was delayed until 8 hours after the CLP procedure, the survival rate was still ∼86% (26/30), compared with 0% in the control group.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

ORIGINAL RESEARCH PAPER

  1. Kaneider, N. C. et al. Reversing systemic inflammatory response syndrome with chemokine receptor pepducins. Nature Medicine 8 May 2005 (10/nm1245)

FURTHER READING

  1. Kuliopulos, A. & Covic, L. Blocking receptors on the inside: pepducin-based intervention of PAR signalling and thrombosis. Life Sci. 74, 255–262 (2005)

    Article  Google Scholar 

Download references

Authors
  1. Alexandra Flemming
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Flemming, A. Pepducins to the rescue. Nat Rev Drug Discov 4, 538–539 (2005). https://doi.org/10.1038/nrd1782

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd1782

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing