Gestational effects on host inflammatory response in normal and pre-eclamptic pregnancies.
OBJECTIVE
Pre-eclampsia (PET) remains a leading cause of maternal and neonatal morbidity and mortality. Although its pathophysiology involves an underlying inflammatory dysfunction, it is unclear how this may be affected by increasing gestational age, particularly in relation to the time of onset of disease. Murine studies have indicated that a progressive increase in serum inflammatory profile is a physiological feature of normal gestation. The present study aimed to investigate this phenomenon in women in relation to normal and pre-eclamptic pregnancies.


METHODS
Control and PET groups (each n=20) were divided into early and late pregnancy (before and after 34 weeks gestation, respectively). Whole blood was diluted 1:1 with RPMI 1640 medium with/without 1 microg/ml lipopolysaccharide at 37 degrees C for 24 h under a humidified 5% CO(2) atmosphere. Samples were collected at 0, 2, 6 and 24 h and analysed for interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, monocyte chemotactic protein (MCP-1), macrophage inflammatory protein (MIP)-1beta and tumour necrosis factor (TNF)-alpha by fluid-phase multiplex immunoassay.


RESULTS
This study confirms that pregnancy features an increasing inflammatory response with advancing gestational age, which was seen in both control and PET pregnancies (P<0.01).


CONCLUSIONS
This increase in inflammatory responsiveness with advancing gestation may provide an explanation for the incidence of late onset PET in the absence of placental pathology, as well as serving as a potential physiological priming mechanism geared towards increasing maternal sensitivity to the fetal triggers of labour.
Brewster
Jennifer A
JA
Perinatal Research Group, The YCR & Liz Dawn Pathology & Translational Sciences Centre, Level 4, Leeds Institute of Molecular Medicine, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Orsi
Nicolas M
NM
Gopichandran
Nadia
N
McShane
Philip
P
Ekbote
Uma V
UV
Walker
James J
JJ
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007249:Inflammation / Q000097:blood; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy
D016207:Cytokines