Inflammatory processes in preterm and term parturition.
A role for the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor alpha (TNF-alpha) is evident in term and preterm delivery, and this is independent of the presence of infection. All uterine tissues progress through a staged transformation near the end of pregnancy that leads from relative uterine quiescence and maintenance of pregnancy to the activation of the uterus that prepares it for the work of labour and production of stimulatory molecules that trigger the onset of labour and delivery. The uterus is activated by pro-inflammatory cytokines through stimulation of the expression and production of uterine activation proteins (UAPs). One of these actions is the stimulation of prostaglandin (PG) synthesis. Particularly important for labour is PGF(2alpha) and its receptor, PTGFR. In addition, pro-inflammatory cytokines are able to increase the synthesis of matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF) and the progesterone receptor C isoform, which leads to decreased tissue progesterone responsiveness. Some of these effects are replicated by PGF(2alpha), suggesting that it may act via its receptor to amplify the direct actions of cytokines. In turn, VEGF may enhance leukocyte recruitment to the uterus, and MMP-9 may promote activation of inactive pro-form cytokines. Pro-inflammatory cytokines also decrease the activity of 11beta-hydroxysteroid dehydrogenase, which likely increases intrauterine cortisol concentrations. In turn, cortisol may drive PG synthesis. Together these feed-forward mechanisms activate the uterus, trigger the production of uterine contractile stimulants and lead to labour and delivery.
Perinatal Research Centre, Departments of Obstetrics and Gynecology, Pediatrics, Physiology, and Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada. Inge@ualberta.ca
Inge
I
Christiaens
Dean B
DB
Zaragoza
Larry
L
Guilbert
Sarah A
SA
Robertson
Bryan F
BF
Mitchell
David M
DM
Olson
D000328:Adult; D016207:Cytokines / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D007231:Infant, Newborn; D007249:Inflammation / Q000209:etiology*; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000276:immunology*; D036801:Parturition / Q000276:immunology*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis; D014599:Uterus / Q000276:immunology*
D016207:Cytokines; D016328:NF-kappa B; D011453:Prostaglandins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006854:Hydrocortisone