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

• DOI: 10.3390/pathogens13010042
• Publication Date: 2023-12-31T11:00:21Z
• Authors: Ines Ambite; Thi Hien Tran; Daniel S. C. Butler; Michele Cavalera; Murphy Lam Yim Wan; Shahram Ahmadi; Catharina Svanborg
• Keywords: uropathogenic <i>Escherichia coli</i>; 0301 basic medicine; 03 medical and health sciences; antibiotic resistance; IL-1 receptor antagonist; R; Medicine; immunotherapy; urinary tract infection; infection; Article

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 innate and restore anti-bacterial defense. E. coli-infected Asc−/− mice develop acute cystitis, defined by IL-1 hyper-activation, high bacterial counts, extensive tissue pathology. Here, interleukin-1 receptor antagonist (IL-1RA), which inhibits hyper-activation in identified as a more potent inhibitor of inflammation NK1R- substance P-dependent pain than cefotaxime. Furthermore, IL-1RA treatment inhibited kidneys infected Irf3−/− restored integrity. Unexpectedly, also accelerated clearance from bladders kidneys, including antibiotic-resistant coli, where cefotaxime inefficient. The results suggest that targeting response, control response infection be regained, with highly favorable outcomes, infections caused strains.