Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits.

Abstract

Serum amyloid A (SAA) is an acute-phase plasma protein which increases 100- to 1000-fold in response to inflammatory stimuli. In this study pregnant rabbits were subjected to laparotomy and their fetuses were injected with lipopolysaccharide (LPS) or various cytokines. Newborn rabbits were likewise stimulated. Hepatic SAA mRNA was studied using Northern blot analyses and scanning densitometry. In vitro derived RNA was used as standard for quantitative mRNA analyses. Cytokine concentrations in amniotic fluid and serum were analysed by biological assays. Fetal rabbits responded to cytokine stimulation by increased hepatic SAA mRNA expression, both during late gestation and in the early neonatal period. However, differences in dose-responses, kinetics and mRNA concentrations were seen dependent on gestational age. IL-1 and tumour necrosis factor (TNF) induced hepatic accumulation of both SAA1, SAA2 and SAA3, while only SAA1 and SAA2 mRNA accumulation was seen after IL-6 stimulation. High levels of IL-1 and TNF found in amniotic fluid from LPS-stimulated fetal rabbits corresponded with high levels in fetal, but not in maternal, serum. High levels of IL-1 and TNF, but no IL-6, were seen in newborn control sera and in adult serum 1 day after a normal delivery. The study details the complexity of the cytokine-induced in vivo response of SAA mRNA in fetal and neonatal rabbits.