Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains
(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.
(Less)
- author
- Ambite, Ines LU ; Tran, Thi Hien LU ; Butler, Daniel S.C. LU ; Cavalera, Michele LU ; Wan, Murphy Lam Yim LU ; Ahmadi, Shahram LU and Svanborg, Catharina LU
- organization
- publishing date
- 2024-01
- 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
-
- pmid:38251349
- scopus:85183163668
- 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
- 2024-04-20 11:01:22
@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}}, }