Anti-inflammatory effects of ceragenin CSA-13 in acute pyelonephritis -insights from an animal model.

Abstract

A hyperactive innate inflammatory response and oxidative stress are the primary contributors to kidney damage in acute pyelonephritis (APN). Consequently, effective APN management requires strategies that target both the bacterial etiology and the host immune response. Here, we report that ceragenin CSA-13, a cholic acid derived antimicrobial compound, is highly effective in treating Escherichia coli-induced model of APN in athymic mice. Specifically, we found that type 17 immunity plays a central role in host defense against E. coli infection, and it can be significantly suppressed by CSA-13 treatment. Thus, the therapeutic effectiveness of CSA-13 is potentially mediated via combination of its direct bactericidal activity and indirect immunomodulation of the host response. CSA-13 significantly reduced bacterial burden in urine and kidney tissue, improved renal histopathology, and lowered serum levels of procalcitonin and KIM-1. Cytokine profiling revealed a reduction of IL-17A, IL-1β, IFN-γ, and GM-CSF, along with increased TIMP-1 levels. Collectively, these findings identify CSA-13 as a dual-action therapeutic candidate capable of attenuating renal inflammation and limiting tissue damage in APN.