Urinary tract infection (UTI) is the most common bacterial infection independent of age. Currently, the gold standard for diagnosis of UTI is based on the presence of bacteria together with white blood cells in the urine to distinguish significant infection vs contamination. Unfortunately, white blood cell count in the urine is non-specific. An ideal biomarker would be elevated in the presence of all UTIs, regardless of causative organism, and not elevated in the absence of UTI, or the presence of systemic inflammatory disease. We hypothesised that interleukin-8 (IL-8), alone or in combination with another reactive protein, is a potential biomarker for UTI.

IL-8, IL-6, Lactoferrin, Uromodulin (Tamm–Horsfall protein-THP). and Procalcitonin levels were measured in urine samples sent to the regional clinical pathology laboratory for microbiology testing where the laboratory confirmed infection with Escherichia coli (n=80), Proteus spp (n=80) or Klebsiella spp (n=80) and culture negative/ no growth (n=75). All assays used were solid-phase sandwich ELISAs from commercial suppliers designed to measure the amount of target bound between a matched antibody pair. Statistical analysis was performed using the Wilcoxon rank sum test with continuity correction and with significance defined as p<0.05.

IL-8 levels were variable for the 3 different causative agents of UTI tested. A significant difference between IL-8 concentrations was seen in samples from healthy volunteers compared with the IL8 concentrations from samples with E.coli or Proteus UTI, or samples sent for investigation that showed no growth (p <0.0001). There was significant difference in the concentrations of IL-8 and lactoferrin between no growth samples and combined UTI samples (p-values of 0.0067 and 0.0005 respectively). For E. coli, lactoferrin showed the most significant difference in the concentrations of the biomarker (p=0.0317); with IL-8 the differences were just outside the significance threshold of 0.05 (p=0.0570). Proteus UTI had the greatest significant difference from the no growth samples for IL-8 (p=0.0020), with lactoferrin also having a significant difference in concentration (p=0.0079). Samples growing Klebsiella had significant differences from the no growth samples for IL-8 (p=0.0344) and lactoferrin (p=0.0079). None of the other biomarkers showed a significant difference between the no growth and UTI groups. Some no growth samples showed increased IL-8.

IL-8 and lactoferrin emerge as promising candidates for distinguishing UTIs and warrant further research to validate the findings and explore the clinical implications for UTI diagnosis and management. Since some no growth samples showed increased IL-8, the possibility of a systemic inflammatory condition raising interleukin levels needs to be excluded. Combined marker measurement may emerge as a strategy to increase sensitivity and specificity.

Il-8 and lactoferrin, alone or in combination, may have the characteristics needed to serve as UTI biomarkers for clinical practice.