Infectious Disease Fellow Nationwide Children's Hospital Dublin, Ohio, United States
Background: Urinary tract infections (UTI) are among the most common bacterial infections encountered in pediatrics. Innate immune defenses, including the secretion of antimicrobial peptides (AMPs) and cytokines into the urinary stream, are crucial for uropathogens clearance and have a pivotal role in preventing UTI. Disrupted AMPs and cytokines expression could provide insight into why some children are predisposed to recurrent UTI (rUTI). The relationship between urinary AMP and cytokine expression in rUTI remains unclear. Objective: Evaluate the concentrations of AMPs and pro-inflammatory cytokines in urine collected from females with a history of rUTI, compared to healthy controls. Design/Methods: Urine was collected from 42 females with rUTI and 38 healthy females. rUTI was defined as having a history of 3 or more culture-positive UTI according to AAP guidelines. Participants ranged from 2-18 years of age. Samples were collected at Nationwide Children’s Hospital outpatient clinics. Urinary AMP and cytokine concentrations were measured via ELISA and normalized to urine creatinine (UCr). Measured AMPs included alpha defensin 1-3 (HNP1-3), beta defensin 1 (HBD1), cathelicidin (LL37), secretory leukocyte protease inhibitor (SLPI), lipocalin 2 (NGAL), and ribonucleases 4 and 7 (RNase 4 and 7). Measured cytokines included IL-1, IL-6, IL-8, and TNFα. Results: Compared to controls, median urinary AMP concentrations of LL37 and RNase 7 were significantly lower in females with rUTI (LL37: 9.42 vs 5.62; RNase 7: 0.79 vs. 0.52 ng/mg UCr). Conversely, HNP1-3 and SLPI concentrations were significantly higher with rUTI (HNP1-3: 1.25 vs 4.1; SLPI 0.63 vs 1.51 ng/ mg UCr). Levels of HBD1, RNase 4 and NGAL did not differ between cohorts (Mann-Whitney). Cytokine concentrations in rUTI samples were 2 to 1,000-fold greater (IL-1 0.65 vs. 0.29; IL-6 22,912 vs. 0.21; IL-8 1243 vs. 4.38; TNFα 110.4 vs. 0.027 ng/mg UCr, p< 0.05, Mann-Whitney).
Conclusion(s): Urine AMPs and cytokines are deregulated in females with rUTI, potentially indicating a compromised immune response that increases UTI susceptibility. These findings may contribute to the development of new tests using AMPs or cytokines as biomarkers to assess UTI risk in children and adolescents.
.jpg "Guillermo Yepes Junquera, MD (he/him/his) photo")
