A Dexamethasone Prodrug Reduces the Renal Macrophage Response and Provides Enhanced Resolution of Established Murine Lupus Nephritis

Autor: Dana E. Tabor, Kimberly K. Bynoté, Jenny S. Nuxoll, Subodh M. Lele, Fang Yuan, Dong Wang, Richard K. Nelson, Yijia Zhang, Hongjiang Yuan, Karen A. Gould
Rok vydání: 2013
Předmět:
Time Factors
Lupus nephritis
lcsh:Medicine
Kidney
Dexamethasone
Mice
0302 clinical medicine
immune system diseases
polycyclic compounds
Prodrugs
lcsh:Science
skin and connective tissue diseases
0303 health sciences
Multidisciplinary
Lupus Nephritis
Immune complex
3. Good health
medicine.anatomical_structure
Hypertension
medicine.symptom
Nephritis
hormones
hormone substitutes
and hormone antagonists
Research Article
medicine.drug
endocrine system
medicine.medical_specialty
Inflammation
03 medical and health sciences
Immune system
White blood cell
Internal medicine
medicine
Albuminuria
Animals
030304 developmental biology
business.industry
Macrophages
lcsh:R
medicine.disease
Survival Analysis
Disease Models
Animal
Endocrinology
Splenomegaly
Immunology
Nephritis
Interstitial
lcsh:Q
business
030215 immunology
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 11, p e81483 (2013)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0081483
Popis: We evaluated the ability of a macromolecular prodrug of dexamethasone (P-Dex) to treat lupus nephritis in (NZB × NZW)F1 mice. We also explored the mechanism underlying the anti-inflammatory effects of this prodrug. P-Dex eliminated albuminuria in most (NZB × NZW)F1 mice. Furthermore, P-Dex reduced the incidence of severe nephritis and extended lifespan in these mice. P-Dex treatment also prevented the development of lupus-associated hypertension and vasculitis. Although P-Dex did not reduce serum levels of anti-dsDNA antibodies or glomerular immune complexes, P-Dex reduced macrophage recruitment to the kidney and attenuated tubulointerstitial injury. In contrast to what was observed with free dexamethasone, P-Dex did not induce any deterioration of bone quality. However, P-Dex did lead to reduced peripheral white blood cell counts and adrenal gland atrophy. These results suggest that P-Dex is more effective and less toxic than free dexamethasone for the treatment of lupus nephritis in (NZB × NZW)F1 mice. Furthermore, the data suggest that P-Dex may treat nephritis by attenuating the renal inflammatory response to immune complexes, leading to decreased immune cell infiltration and diminished renal inflammation and injury.
Databáze: OpenAIRE
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