Background Progesterone-induced blocking factor 1 (PIBF1), a protein produced by maternal lymphocytes upon exposure to progesterone during pregnancy, acts as an immunomodulator by suppressing several immune pathway cytokines including Th1-based cytokines. Considering the female susceptibility to systemic lupus erythematosus, we aimed to determine the role of recombinant PIBF1 in the alleviation of lupus nephritis (LN) in MRL/MpJ-Faslpr/J (MRL/lpr) mice.
Methods MRL/lpr mice were ovariectomized at 6 weeks of age, and recombinant PIBF1 was administered intraperitoneally from 8 to 26 weeks of age (twice a week). Serum anti-dsDNA level was examined every 2 weeks from 8 to 24 weeks of age. The levels of serum cytokines at 16 and 24 weeks of age and urine albumin/creatinine (uACR) at 26 weeks of age were measured. At 26 weeks, the mice were sacrificed, and kidney biopsy was performed. Pathologic grading of disease activity and chronicity was performed by an animal pathologist according to the criteria of the NIH activity and chronicity indices. Additionally, splenocytes were analyzed by flow cytometry.
Results Serum anti-dsDNA level was increased in MRL/lpr mice that underwent ovariectomy; however, recombinant PIBF1 treatment attenuated the increase in anti-dsDNA autoantibodies (statistical significance after 18 weeks, p <0.05). uACR at 26 weeks was significantly decreased in the PIBF1-treated ovariectomy group compared with the PIBF1-untreated ovariectomy group (p <0.05). Furthermore, interstitial inflammation, global glomerulosclerosis, total activity index, and chronicity index scores were significantly decreased in PIBF1-treated mice compared with non-treated mice (figure 1). Analysis of splenocytes revealed that B220+CD4-CD8- T cells were decreased in PIBF1-treated mice compared with non-treated mice (p <0.05). However, the levels of serum cytokines including IL-2, IL-10, and IL-21 were not different between the two groups.
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