Labour-associated changes in the regulation of production of immunomodulators in human amnion by glucocorticoids, bacterial lipopolysaccharide and pro-inflammatory cytokines

Parturition is associated with changes in the production of inflammatory me diators 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 spont aneous vaginal delivery (n = 3-7). After 24 h equilibration in media, the t issues were treated with interleukin 1 beta (10 ng ml(-1)), tumour necrosis factor alpha (100 ng ml(-1)), lipopolysaccharide (5 mu g ml(-1)) and dexam ethasone (1 mu mol 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 E-2 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 PGE(2) by amnion explants were significantly higher (P < 0.0012; Mann-Whitney U test) in tissues taken during labour than in tissu es taken before the onset of labour, while interleukin 6 production was not significantly altered by labour. Production rates of interleukin 6 and pro staglandin E-2 were significantly increased by interleukin 1 beta, tumour n ecrosis factor alpha and lipopolysaccharide in explants from tissues taken during and before labour, while the responsiveness of interleukin 10 produc tion to these treatments was inconsistent. Dexamethasone had no effect on i nterleukin 6 production by amnion explants, but significantly inhibited pro staglandin E-2 production, although this inhibition was approximately 30% l ower in tissues obtained after the onset of labour. These results support t he presence of inflammatory positive feedback cycles, coincident with a def iciency of an anti-inflammatory factor within gestational tissue, which may be involved in the progression or maintenance of labour.