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. 2013 Dec;20(12):1447-54.
doi: 10.1177/1933719113488445. Epub 2013 May 7.

Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone

Affiliations

Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone

Katherine B Wolfe et al. Reprod Sci. 2013 Dec.

Abstract

Objective: We tested the hypothesis that the order of exposure to maternal betamethasone and intra-amniotic (IA) lipopolysaccharide (LPS) will differentially modulate inflammation in the chorioamnion.

Study design: Time-mated Merino ewes with singleton fetuses received saline alone, IA LPS alone, maternal betamethasone before LPS, or betamethasone after LPS. We assessed inflammatory markers in the chorioamnion and the amniotic fluid.

Results: Inflammatory cell infiltration, expression of myeloperoxidase, serum amyloid A3 (acute phase reactant) in the chorioamnion, and levels of interleukin (IL)-8 in the amniotic fluid increased 7 days after LPS exposure. Betamethasone prior to LPS decreased infiltration of the inflammatory cells, CD3+ T cells, and decreased the levels of IL-1β and IL-8 in the amniotic fluid.

Conclusions: Betamethasone 7 days prior to LPS exposure suppressed LPS-induced inflammation. The markers of inflammation largely had returned to the baseline 14 days after LPS exposure.

Keywords: innate immunity; prematurity; preterm labor.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Maternal β-methasone (β) prior to intra-amniotic lipopolysaccaride (LPS) blunts histologic chorioamnionitis (A). Scores indicating severity of histologic chorioamnionitis are shown for the different groups. Representative photomicrographs of hematoxylin and eosin staining are shown for (B) Saline 14 days/Saline 7 days (control), (C) Saline14 days/LPS 7 days, (D) Beta 14 days/LPS 7 days, (E) LPS 14 days/Saline 7 days, and (F) LPS 14 days/β 7 days groups. Arrows indicate inflammatory cells and arrow heads identify the amniotic epithelium. Note the thickened amnion and sloughing of amniotic epithelium in (C). N = 4-6 animals/group, scale bar (B) represents 50 µm, *P < .05 versus saline 14 days/saline 7 days, #P < .05 versus Saline14 days/LPS 7 days.
Figure 2.
Figure 2.
Myeloperoxidase (MPO) expression in inflammatory cells after maternal β-methasone (β) and intra-amniotic lipopolysaccharide (LPS; A). Mean MPO-expressing cells per microscopic field are shown for the different groups. Representative photomicrographs of MPO immunostaining are shown for (B) Saline 14 days/Saline 7 days (control), (C) Saline14 days/LPS 7 days, (D) β 14 days/LPS 7 days, (E) LPS 14 days/Saline 7 days, and (F) LPS 14 days/β 7 days groups. Arrows point to MPO-expressing cells. N = 4-6 animals/group, scale bar (B) represents 50 µm, *P < .05 versus Saline 14 days/Saline 7 days.
Figure 3.
Figure 3.
Maternal β-methasone (β) prior to intra-amniotic lipopolysaccharide (LPS) blunts infiltration of CD3+ T cells in the chorioamnion (A). Mean CD3-expressing cells per microscopic field are shown for the different groups. Representative photomicrographs of CD3 immunostaining are shown for (B) Saline 14 days/Saline 7 days (control), (C) Saline14 days/LPS 7 days, (D) β 14 days/LPS 7 days, (E) LPS 14 days/Saline 7 days, and (F) LPS 14 days/β 7 days groups. Arrows point to CD3-expressing cells in (C). N = 4 animals/group, scale bar (B) represents 50 µm, *P < .05 versus Saline 14 days/Saline 7 days, #P < .05 versus Saline14 days/LPS 7 days.
Figure 4.
Figure 4.
Maternal β-methasone (β) prior to intra-amniotic lipopolysaccharide (LPS) blunts expression of proinflammatory cytokines/chemokines in the amniotic fluid. Amniotic fluid cytokines were quantitated using enzyme-linked immunosorbent assay (ELISA). A, IL-1β, (B) IL-6, and (C) IL-8. Compared to the saline 14 days/LPS group, β 14 days/LPS 7 days animals had lower IL-1β and IL-8 levels. N = 4-6 animals/group, *P < .05 versus saline 14 days/saline 7 days, # P < .05 versus saline14 days/LPS 7 days.

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