Urinary tract infections activate a mucosal inflammatory response, which includes cytokine secretion and neutrophil influx. The mechanisms involved in the neutrophil influx have not been identified. Interleukin-8, a potent chemoattractant for neutrophils, is produced by urinary tract epithelial cell lines in vitro. This study analyzed the human IL-8 response to deliberate Escherichia coli infection of the urinary tract. Urine and serum samples were obtained before and after intravesical instillation of E. coli. Neutrophil numbers were determined on uncentrifuged urine, and IL-8 levels were measured by ELISA. A urinary IL-8 response was found in all patients after bacterial instillation, but no serum IL-8 was detected. There was a strong correlation between urinary IL-8 levels and urinary neutrophil numbers. The same E. coli strains used to colonize the patients stimulated IL-8 production in urinary tract epithelial cells. The level of IL-8 secreted by epithelial cell lines was influenced by the fimbrial properties of the E. colt. These results demonstrated that E. coli elicit a mucosal IL-8 response in humans, and suggested that IL-8 is involved in the onset of pyuria. Epithelial cells may be an important source of IL-8 during urinary tract infection. (J. Clin. Invest. 1993. 92:780-785.)

Women with intermediate flora generate significant cytokine responses. It is possible that the risks associated with BV may also affect women with intermediate flora and that appropriate treatment may reduce such risk.

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The levels of interleukin (IL)-1, IL-6, IL-8, IL-10, and transforming growth factor-beta in sera and genital tract secretions from women with gonococcal cervicitis and other genital infections were examined. Cytokines were not elevated in genital secretions from gonococcus-infected compared with uninfected patients. The level of serum IL-6 was higher in gonococcus-infected than in uninfected patients at recruitment. Serum, but not local, IL-1 and IL-6 levels were elevated in patients concomitantly infected with Trichomonas vaginalis or Chlamydia trachomatis in addition to Neisseria gonorrhoeae compared with levels in patients infected with any single organism. Concomitant infection altered neither the total immunoglobulin concentrations nor the levels of antigonococcal antibodies in serum or local secretions. The results suggest that N. gonorrhoeae induces only a limited cytokine and antibody response during uncomplicated cervical infections; however, the presence of other sexually transmitted disease-causing organisms can alter the systemic cytokine but not the antigonococcal antibody levels.

This study demonstrated that epithelial cell lines secrete interleukin-6 (IL-6) in response to stimulation with gram-negative bacteria. Human epithelial cell lines of urinary tract origin (A-498 and J82) and of intestinal origin (HT-29 and Caco-2) were analyzed for the secretion of IL-6 by using the B9 bioassay. The supernatants from cells maintained with culture medium were used to assess the constitutive production of IL-6. The supernatants from cells exposed to Escherichia coli strains, lipopolysaccharide, lipid A, and isolated fimbriae were used to quantitate the IL-6 response to these stimulants. The urinary tract epithelial cell lines were found to constitutively secrete IL-6. The IL-6 activity in the supernatants of the bladder cell line (J82) increased above constitutive levels after 2 h of stimulation by most of the bacterial strains tested. The IL-6 activity in the supernatants of the kidney line (A-498) accumulated at a constant rate over the 24-h assay period. The role of bacterial adherence for the induction of IL-6 production was investigated by comparing the responses to recombinant E. coli strains expressing different fimbriae. In addition, isolated P and S fimbriae wth and without the receptor binding domain were also used as stimulants. The IL-6 activity in the supernatants of the bladder cell line increased after exposure to bacteria and bacterial products regardless of their adhesive properties. In contrast, the kidney cell line was stimulated to secrete significantly more IL-6 by adhering bacteria and by adhesin-positive P fimbriae than by nonadhering bacteria or adhesin-negative P fimbriae. The S-fimbrial preparations had no specific effects on the IL-6 activity of the cell supernatants. These results are consistent with our hypothesis that epithelial cells can be a major source of IL-6 when stimulated by bacteria and that the adhesive properties of the bacteria can influence this response.