RRC ID 77815
Author Ines Ambite, Thi Hien Tran, Daniel S. C. Butler, Michele Cavalera, Murphy Lam Yim Wan, Shahram Ahmadi, Catharina Svanborg
Title Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains
Journal Pathogens
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.
Volume 13
Pages 42
Published 2023-12-31
DOI 10.3390/pathogens13010042
PMID 38251349
PMC PMC10820880
IF 3.018
Mice RBRC00858