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Failure of dexamethasone to prevent polymorphonuclear leukocyte infiltration during experimental acute exudative
1Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Abstract:
In experimental acute exudative pyelonephritis (AEP), a role for polymorphonuclear leukocyte (PMNL) infiltration in the pathogenesis of kidney scarring has been suggested indirectly. To directly quantitate PMNL infiltration during AEP, we developed an assay for measuring the content in the kidney of myeloperoxidase (MPO), an enzyme present in PMNLs and absent in kidney tissue. This assay was a specific and sensitive marker of the kidney PMNL content. We used this assay to measure in rats with AEP the effect of dexamethasone, administered in an attempt to mitigate the acute inflammatory response. Compared with saline, dexamethasone given during AEP strikingly reduced kidney swelling, measured by the kidney-weight increase, but failed to reduce PMNL infiltration, measured by the kidney MPO content. Despite reduced kidney swelling during AEP, dexamethasone treatment failed to prevent subsequent kidney scarring, an observation indicating that PMNLs play a role in the development of permanent kidney damage during AEP.
Insights
Polymorphonuclear leukocytes (PMNLs) contribute to kidney scarring in acute exudative pyelonephritis (AEP). Dexamethasone reduced swelling but not PMNL infiltration, confirming PMNLs
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Kidney scarring in acute exudative pyelonephritis (AEP) may involve polymorphonuclear leukocyte (PMNL) infiltration.
- Direct quantification of PMNLs in kidney tissue during AEP has been lacking.
Purpose of the Study:
- To develop and validate an assay for quantifying kidney PMNLs in AEP.
- To investigate the effect of dexamethasone on PMNL infiltration and kidney scarring in a rat model of AEP.
Main Methods:
- Developed a myeloperoxidase (MPO) assay to measure kidney PMNL content in rats with AEP.
- Administered dexamethasone to assess its impact on kidney swelling, PMNL infiltration (MPO levels), and subsequent scarring.
Main Results:
- The MPO assay proved to be a specific and sensitive marker for kidney PMNLs.
- Dexamethasone significantly reduced kidney swelling but did not decrease MPO levels (PMNL infiltration).
- Dexamethasone treatment failed to prevent kidney scarring despite reduced swelling.
Conclusions:
- PMNLs play a direct role in the pathogenesis of kidney scarring during AEP.
- Reducing kidney swelling with dexamethasone does not necessarily mitigate PMNL-driven damage or prevent scarring.