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Vol. 284, Issue 3, 1203-1208, March 1998
Section of Urology and Department of Pharmacology, Yale University
School of Medicine, New Haven, Connecticut
Systemic bacterial lipopolysaccharides (LPS) induce inflammatory
responses characteristic of sepsis. Instillation of LPS into rat
bladder produces a localized inflammatory response similar to that seen
in urinary tract infections (UTIs). Four hours after intravesical
instillation of LPS, neutrophils infiltrate into the bladder, and mRNA
for inducible nitric oxide synthase (iNOS) and the cytokines,
interleukin (IL)-6 and IL-10, is detected in rat bladder but not in the
kidney. Induction of iNOS protein is inferred because urinary nitrate
and cGMP levels are increased 4 hr after LPS intravesical instillation
and remain elevated for at least 24 hr. When LPS is injected
intraperitoneally, iNOS and IL-6 mRNA are induced both in the bladder
and in the kidney. These data are consistent with the effects of
intravesical instillation of LPS remaining localized. iNOS activity
increases in both particulate and soluble bladder fractions when
measured 4 hr after intravesical instillation of LPS. The magnitude of
these increases in iNOS activity in the bladder is not as great as when
LPS is injected intraperitoneally. Intravesical instillation of LPS
induces no increase in lung or kidney NOS activity. The localized
inflammatory response produced by intravesical instillation of LPS
demonstrates the importance of LPS as a mediator of the host response
in UTIs and supports the use of urinary measurements of nitrate and
cGMP in humans as indicative of the localized induction of iNOS in UTIs.
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