The mucosal cytokine response to urinary tract infections.
This review focussed on the cytokine responses to urinary tract infections. Colonization of the human urinary tract with E. coli activates the intermittant secretion of IL-6 and IL-8 into urine. In contrast, local bacterial challenge did not give rise to detectable serum IL-6 or IL-8 levels. IL-6 is detected in the urine at the time of diagnosis in most patients with natural urinary tract infections; however, IL-6 was only detected in the serum of symptomatic patients. These observations suggested that the cytokine response during UTI can have local and systemic components. Epithelial cells have been examined as a likely source of the local cytokines produced in response to UTI. The profile of cytokines produced by uroepithelial cells in response to E. coli is similar to that secreted during UTI (IL-6 and IL-8, but no IL-1 or TNF). Adhering bacteria and isolated P fimbriae stimulate higher levels of IL-6 production in cells that express the globoseries of glycolipids such as kidney epithelial cells. Uroepithelial cells also respond to stimulation by cytokines; IL-1alpha and TNFalpha induce the secretion of IL-6 and IL-8 and the upregulation of mRNAs for IL-1alpha, IL-1beta, IL-6 and IL-8. This cytokine profile is similar to that detected after bacterial stimulation; however, the magnitude and kinetics of the epithelial cell cytokine responses differed between the stimulants. Interleukin-4 induced epithelial cell IL-6 and IL-8 production; gamma-interferon only induced IL-6 production. This suggests that epithelial cells produce primary and secondary cytokine responses, and can function in mucosal cytokine networks with a variety of cells. Cytokines are mediators of immune functions and inflammation and it is likely that the local cytokine production influences both the induction of symptoms as well as the eventual outcome of the infection. Examination of local cytokine levels during UTI may prove to be a useful diagnostic tool; however, this possibility requires further evaluation.
Hedges
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Department of Medical Microbiology, Section of Clinical Immunology, University of Lund, S-223 46 Lund, Sweden.
Svanborg
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