| First Author | Ambite I | Year | 2023 |
| Journal | Pathogens | Volume | 13 |
| Issue | 1 | PubMed ID | 38251349 |
| Mgi Jnum | J:347075 | Mgi Id | MGI:7620576 |
| Doi | 10.3390/pathogens13010042 | Citation | Ambite I, et al. (2023) Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains. Pathogens 13(1) |
| abstractText | 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. |
