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Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains

Ambite, Ines LU orcid ; Tran, Thi Hien LU ; Butler, Daniel S.C. LU ; Cavalera, Michele LU ; Wan, Murphy Lam Yim LU orcid ; Ahmadi, Shahram LU and Svanborg, Catharina LU (2024) In Pathogens 13(1).
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acute cystitis, acute pyelonephritis, antibiotic resistance, IL-1, IL-1 receptor antagonist, immunotherapy, infection, substance P, urinary tract infection, uropathogenic Escherichia coli
in
Pathogens
volume
13
issue
1
article number
42
publisher
MDPI AG
external identifiers
  • scopus:85183163668
  • pmid:38251349
ISSN
2076-0817
DOI
10.3390/pathogens13010042
language
English
LU publication?
yes
id
00af5ffe-86f6-4ec3-9fbc-491933a407e8
date added to LUP
2024-02-20 11:48:42
date last changed
2025-11-17 15:27:22
@article{00af5ffe-86f6-4ec3-9fbc-491933a407e8,
  abstract     = {{<p>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<sup>−/−</sup> 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<sup>−/−</sup> 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.</p>}},
  author       = {{Ambite, Ines and Tran, Thi Hien and Butler, Daniel S.C. and Cavalera, Michele and Wan, Murphy Lam Yim and Ahmadi, Shahram and Svanborg, Catharina}},
  issn         = {{2076-0817}},
  keywords     = {{acute cystitis; acute pyelonephritis; antibiotic resistance; IL-1; IL-1 receptor antagonist; immunotherapy; infection; substance P; urinary tract infection; uropathogenic Escherichia coli}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{Pathogens}},
  title        = {{Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains}},
  url          = {{http://dx.doi.org/10.3390/pathogens13010042}},
  doi          = {{10.3390/pathogens13010042}},
  volume       = {{13}},
  year         = {{2024}},
}