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Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria
H Linder1, I Engberg, C van Kooten
1Department of Clinical Immunology, University of Göteborg, Sweden.
Abstract:
Gram-negative bacterial infections of the urinary tract elicit a mucosal inflammatory response. Interleukin-6 is secreted into the urine, and polymorphonuclear leukocytes (PMNL) are recruited. In the present study we examined the effect of anti-inflammatory agents on these parameters and on bacterial clearance from the kidneys. Dexamethasone reduced interleukin-6 secretion, the PMNL response, and bacterial clearance. Diclofenac abolished the urinary interleukin-6 response but reduced the PMNL response and bacterial clearance only at the highest concentrations. Indomethacin drastically decreased bacterial clearance without the corresponding effect on interleukin-6 production or the PMNL response. The results demonstrate that the inhibition of inflammation impairs bacterial clearance from the kidneys. This is, however, not a direct function of inhibited interleukin-6 production or PMNL recruitment.
Insights
Anti-inflammatory drugs impair bacterial clearance from kidneys during Gram-negative infections. While these agents reduce inflammation markers like interleukin-6 and polymorphonuclear leukocytes, they hinder the body's ability to fight infection.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Gram-negative bacterial urinary tract infections (UTIs) trigger significant mucosal inflammation.
- Key inflammatory markers include urinary interleukin-6 (IL-6) and polymorphonuclear leukocyte (PMNL) recruitment.
Purpose of the Study:
- To investigate the impact of anti-inflammatory agents on inflammatory responses and bacterial clearance in the kidneys during Gram-negative UTIs.
- To determine if inhibiting inflammation directly affects bacterial clearance.
Main Methods:
- Administration of dexamethasone, diclofenac, and indomethacin to infected models.
- Measurement of urinary IL-6 levels.
- Quantification of PMNL infiltration.
- Assessment of bacterial load in kidney tissue.
Main Results:
- Dexamethasone suppressed IL-6, PMNLs, and bacterial clearance.
- Diclofenac abolished IL-6 response but only reduced PMNLs and clearance at high doses.
- Indomethacin significantly impaired bacterial clearance without affecting IL-6 or PMNLs.
Conclusions:
- Inhibition of inflammation negatively impacts bacterial clearance from the kidneys.
- This impairment is not solely attributable to reduced IL-6 production or PMNL recruitment.