Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains.
Pathogens
; 13(1)2023 Dec 31.
Article
em En
| MEDLINE
| ID: mdl-38251349
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Pathogens
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Suécia