MRL-lpr/lpr mice spontaneously develop an autoimmune disease with nephritis similar to human systemic lupus erythematosus. In these animals, treatment with E-series prostaglandins ameliorates renal disease and prolongs survival, perhaps by modulating production of cytokines or eicosanoids. To further define the mechanisms of action of E-series prostaglandins in established murine lupus nephritis, we administered the prostaglandin E, (PGE1) analog misoprostol to 20-week-old MRL-lpr/lpr mice by twice-daily subcutaneous injection. After 2 days of treatment, misoprostol reduced renal cortical interleukin-1β (IL-1P) mRNA levels compared to vehicle-treated controls (0.19 ± 0.06 (misoprostol) vs 0.50 ± 0.04 (vehicle) densitometry units; P < 0.005). A similar reduction in cortical IL-1P mRNA levels was found in left kidneys harvested from MRL-lpr/lpr mice following 2 days of treatment with misoprostol compared to right kidneys harvested from the same animal prior to the first dose of PGE1, analog (0.12 ± .05 (left) vs 0.39 ± 0.18 (right) densitometry units; P < 0.05). This reduction in cortical IL-1β mRNA levels was not associated with alterations in renal production of thromboxane B2, PGE2, or leukotriene B4 or with significant changes in the severity of renal inflammatory cell infiltrates. Timecourse studies indicated that IL-1P mRNA levels were decreased within 24 hr of initiating misoprostol therapy. This reduction in IL-1β mRNA levels was transient because levels were not reduced after 1 week of treatment with the PGE1 analog. Thus, while the beneficial effects of chronic treatment with E-series prostaglandins in MRL-lpr/lpr mice may be mediated by other mechanisms, these data suggest than an important short-term effect of misoprostol in this model may be suppression of renal cortical IL-1P mRNA levels.
ASJC Scopus subject areas
- Immunology and Allergy
- Pathology and Forensic Medicine