Therapeutic effects of IL-1RA against acute bacterial infections, including antibiotic-resistant strains

Ines Ambite, Thi Hien Tran, Daniel Butler, Michele Cavalera, Murphy Wan, Shahram Ahmadi, Catharina Svanborg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Innate immunity is essential for the anti-microbial defense, but excessive immune activation may cause severe disease. In this study, immunotherapy was shown to prevent excessive innate immune activation and restore the anti-bacterial defense. E. coli-infected Asc−/− mice develop severe acute cystitis, defined by IL-1 hyper-activation, high bacterial counts, and extensive tissue pathology. Here, the interleukin-1 receptor antagonist (IL-1RA), which inhibits IL-1 hyper-activation in acute cystitis, was identified as a more potent inhibitor of inflammation and NK1R- and substance P-dependent pain than cefotaxime. Furthermore, IL-1RA treatment inhibited the excessive innate immune activation in the kidneys of infected Irf3−/− mice and restored tissue integrity. Unexpectedly, IL-1RA also accelerated bacterial clearance from infected bladders and kidneys, including antibiotic-resistant E. coli, where cefotaxime treatment was inefficient. The results suggest that by targeting the IL-1 response, control of the innate immune response to infection may be regained, with highly favorable treatment outcomes, including infections caused by antibiotic-resistant strains.
Original languageEnglish
Article number42
Number of pages18
JournalPathogens
Volume13
Issue number1
DOIs
Publication statusPublished - 31 Dec 2023

Keywords

  • infection
  • immunotherapy
  • antibiotic resistance
  • urinary tract infection
  • uropathogenic Escherichia coli
  • IL-1 receptor antagonist
  • IL-1
  • substance P
  • acute cystitis
  • acute pyelonephritis

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