title: Labour-associated changes in the regulation of production of immunomodulators in human amnion by glucocorticoids, bacterial lipopolysaccharide and pro-inflammatory cytokines.
abstract: Parturition is associated with changes in the production of inflammatory mediators by gestational tissues. An explant system was established to study the change in response of human amnion to various regulating factors during labour. Disks of tissue (6 mm) were excised from amnion membranes obtained either at term by Caesarian section before labour (n = 5-6) or after spontaneous vaginal delivery (n = 3-7). After 24 h equilibration in media, the tissues were treated with interleukin 1 beta (10 ng ml-1), tumour necrosis factor alpha (100 ng ml-1), lipopolysaccharide (5 micrograms ml-1) and dexamethasone (1 mumol l-1) or an appropriate vehicle control for 24 h (n = 3 wells per treatment). Media were harvested and interleukin 10, interleukin 6 and prostaglandin E2 concentrations were determined by immunoassay. In tissues taken both before and after the onset of labour, basal interleukin 10 production by amnion explants was near to the limit of detection. Basal production rates of PGE2 by amnion explants were significantly higher (P < 0.0012; Mann-Whitney U test) in tissues taken during labour than in tissues taken before the onset of labour, while interleukin 6 production was not significantly altered by labour. Production rates of interleukin 6 and prostaglandin E2 were significantly increased by interleukin 1 beta, tumour necrosis factor alpha and lipopolysaccharide in explants from tissues taken during and before labour, while the responsiveness of interleukin 10 production to these treatments was inconsistent. Dexamethasone had no effect on interleukin 6 production by amnion explants, but significantly inhibited prostaglandin E2 production, although this inhibition was approximately 30% lower in tissues obtained after the onset of labour. These results support the presence of inflammatory positive feedback cycles, coincident with a deficiency of an anti-inflammatory factor within gestational tissue, which may be involved in the progression or maintenance of labour.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, New Zealand.
authors.forename: K L
authors.initials: KL
authors.lastname: Simpson
authors.forename: J A
authors.initials: JA
authors.lastname: Keelan
authors.forename: M D
authors.initials: MD
authors.lastname: Mitchell
mesh_terms: D000276:Adjuvants, Immunologic / Q000032:analysis*; D000650:Amnion / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005246:Feedback; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007743:Labor, Obstetric / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011247:Pregnancy; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone; D015232:Dinoprostone