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Elevated interleukin-8 levels in the urine of patients with urinary tract infections
Y C Ko1, N Mukaida, S Ishiyama
1Department of Clinical Pathology, Jichi Medical School, Tochigi-ken, Japan.
Abstract:
Pyuria is one of the main features of urinary tract infections (UTI). Nevertheless, the mechanism of polymorphonuclear leukocyte (PMN) recruitment into the urine remains to be investigated. We examined whether interleukin-8 (IL-8), a potent neutrophil chemoattractant and activator, was involved in pyuria seen in UTI. Of 113 patients, 112 had elevated levels of IL-8 in their urine (1,078.0 +/- 181.5 pg/ml), regardless of whether they had an upper or lower UTI; this was in contrast to undetectable levels (less than 16 pg/ml) in the urine of all of the 20 normal individuals and 74 control patients without UTI. A concomitant study revealed increases in urine IL-6, but not IL-1 beta, and tumor necrosis factor alpha levels in patients with UTI. In addition to gram-negative bacteria, a wide spectrum of microorganisms was capable of inducing IL-8 production in urine. Local production of IL-8 in the urinary tract was suggested by a urine IL-8 level that was higher than the paired serum IL-8 level. The urine IL-8 level correlated with the number of PMN in the urine, and an average of half of the chemotactic activity in urine from patients with UTI could be abrogated by anti-IL-8 antibody treatment in vitro. Furthermore, urine IL-8 purified from patients was bioactive and showed multiple forms on immunoblotting analysis. This is the first documentation of IL-8 in the urine of patients with UTI, and these results imply that IL-8 is involved in inducing PMN migration into the urinary tract.
Insights
Interleukin-8 (IL-8) is elevated in the urine of patients with urinary tract infections (UTI), driving polymorphonuclear leukocyte (PMN) recruitment and contributing to pyuria. This study confirms IL-8
Area of Science:
- Immunology
- Microbiology
- Urology
Background:
- Pyuria, a hallmark of urinary tract infections (UTI), involves polymorphonuclear leukocyte (PMN) infiltration.
- The precise mechanisms governing PMN recruitment into the urinary tract during UTI are not fully understood.
Purpose of the Study:
- To investigate the role of interleukin-8 (IL-8), a key neutrophil chemoattractant, in the pyuria observed in UTI patients.
- To determine if IL-8 levels correlate with UTI severity and microbial presence.
Main Methods:
- Quantification of IL-8 levels in urine samples from 113 UTI patients and 94 controls using ELISA.
- Analysis of other inflammatory cytokines, including IL-6, IL-1 beta, and TNF-alpha.
- In vitro experiments assessing the effect of anti-IL-8 antibodies on urine chemotactic activity.
Main Results:
- 112 out of 113 UTI patients exhibited significantly elevated urine IL-8 levels compared to undetectable levels in controls.
- Urine IL-8 levels correlated positively with PMN counts and demonstrated local production within the urinary tract.
- Microorganisms, including Gram-negative bacteria, stimulated IL-8 production in urine.
Conclusions:
- Interleukin-8 (IL-8) is a critical mediator of polymorphonuclear leukocyte (PMN) migration into the urinary tract during infections.
- Elevated urine IL-8 levels are a consistent finding in UTI and contribute significantly to pyuria.
- IL-8 represents a potential therapeutic target for managing UTI-associated inflammation.