Cytokine Profiles of Pediatric Patients Treated with Antibiotics for Pyelonephritis: Potential Therapeutic Impact

Abstract

Urinary tract infections are common in infants and children. Pyelonephritis may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the timing of release of inflammatory cytokines in relation to pyelonephritis and its treatment is essential for designing interventions that would minimize tissue damage. To this end, we measured urinary cytokine concentrations of interleukin-1␤ (IL-1␤), IL-6, and IL-8 in infants and children with pyelonephritis and in healthy children. Children that presented to our institution with presumed urinary tract infection were given the diagnosis of pyelonephritis if they had a positive urine culture, pyuria, and one or more of the following indicators of systemic involvement: fever, elevated peripheral white blood cell count, or elevated C-reactive protein. Urine samples were obtained at the time of presentation prior to the administration of antibiotics, immediately after completion of the first dose of antibiotics, and at follow up 12 to 24 h after presentation. IL-1␤, IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assay. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between preantibiotic and follow-up cytokine/creatinine ratios were significant for IL-1␤, IL-6, and IL-8 (P < 0.01). Differences between preantibiotic and control cytokine/creatinine ratios were also significant for IL-1␤, IL-6, and IL-8 (P < 0.01). Our study revealed that the urinary tract cytokine response to infection is intense but dissipates shortly after the initiation of antibiotic treatment. This suggests that renal damage due to inflammation begins early in infection, underscoring the need for rapid diagnosis and intervention.

Cytokines in urine in elderly subjects with acute cystitis and asymptomatic bacteriuria

“…Except for higher levels of TNF-a and IL-12, and lower levels of IL-18 in the ASB group as compared with negative controls, we found no differences between the groups with regard to the pro-inflammatory cytokines IL-1b, TNF-a, IL-12, and IL-18, and this is in accordance with the findings of others [13,22,23].…”

Serum and Urinary MIP-1α and IP-10 Levels in Children with Urinary Tract Infections

“…IL-6 promotes the growth and differentiation of T and B lymphocytes. Kassir et al reported that elevated IL-6 confirmed the inflammatory process, and that IL-6 levels rapidly decreased after appropriate antibiotic treatment [6]. The findings in the current study are not consistent with this observation.…”

“…Some authors have attempted to identify markers of inflammation in urine and to use them in the diagnosis of infection of the urinary tract and in monitoring response to therapy [3][4][5][6].…”

Evaluation and Comparison of Urinary Cytokines for the Diagnosis of Acute Pyelonephritis

“…They are involved in B cell and T cell proliferation and neutrophil chemoattraction, along with secretion of CRP, immunoglobulins, and acute-phase proteins (2,6,8,10) Clinical manifestations of APN depend on the production of different cytokines, and measurement of urinary ILs seems to be useful for the rapid diagnosis and localization of inflammation within the urinary tract system. Increased urinary IL-1, IL-4, IL-6, and IL-8 concentrations have been reported in children with acute febrile UTIs compared to the healthy children and those with lower UTIs, asymptomatic bacteriuria, and non-renal febrile infections (2,(11)(12)(13)(14)(15).…”

“…Therefore, the determination of urinary ILs is helpful for the evaluation of treatment response in APN, and persistently elevated urinary IL concentrations indicate treatment modifications (6,9,17). Accordingly, increased urinary IL levels decreased following antibiotic treatment and were considered for therapeutic monitoring in our patients.…”