The effects of short-term treatment with the prostaglandin E1 (PGE1) analog misoprostol on inflammatory mediator production in murine lupus nephritis.
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 E1 (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-1 beta (IL-1 beta) 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-1 beta 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-1 beta 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. Time-course studies indicated that IL-1 beta mRNA levels were decreased within 24 hr of initiating misoprostol therapy. This reduction in IL-1 beta mRNA levels was transient because levels were not reduced after 1 week of treatment with the PGE1 analog.(ABSTRACT TRUNCATED AT 250 WORDS)
Fan
P Y
PY
Department of Medicine, Duke University, Durham, North Carolina 27710, USA.
Ruiz
P
P
Pisetsky
D S
DS
Spurney
R F
RF
D000818:Animals; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000235:genetics; D007668:Kidney / Q000737:chemistry; D008181:Lupus Nephritis / Q000188:drug therapy*; D051379:Mice; D008817:Mice, Mutant Strains; D016595:Misoprostol / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors
D007375:Interleukin-1; D012333:RNA, Messenger; D016595:Misoprostol