title: Maternal plasma cytokines in early- and mid-gestation of normal human pregnancy and their association with maternal factors.
abstract: Few studies have assessed longitudinal changes in circulating cytokine levels during normal pregnancy. We have examined the natural history of maternal plasma cytokines from early- to mid-pregnancy in a large, longitudinal cohort. Multiplex flow cytometry was used to measure interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) in early- (median [IQR]: 8.5 weeks [7.1, 10.0]) and mid-pregnancy (25.0 [24.1, 26.1]) from 1274 Danish women delivering singleton term infants. GM-CSF decreased from early- to mid-pregnancy (median percent change [95% CI]: -51.3% [-59.1%, -41.8%]), while increases were observed in IL-6 (24.3% [4.6%, 43.9%]), IL-12 (21.3% [8.9%, 35.7%]) and IFN-gamma (131.7% [100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) and TNF-alpha (0% [-5.9%, 25.6%]) remained stable. Positive correlations were found between all cytokines, both in early- and mid-pregnancy (all p<0.001). Early- and mid-pregnancy levels were rank-correlated for IL-2, IL-12, TNF-alpha and GM-CSF, but not IL-6 and IFN-gamma; these correlations were generally weaker than correlations between different cytokines at a single time point in pregnancy. Women with a pre-pregnancy BMI <18.5 had reduced levels of IFN-gamma and GM-CSF compared to women in other BMI categories, while women aged >or=35 years had elevated IL-2, IL-6, TNF-alpha and IFN-gamma. Early-pregnancy levels of TNF-alpha were higher in women with a prior preterm delivery. Cytokine levels were not associated with gravidity. In conclusion, cytokines were detected in plasma during early- and mid-pregnancy, with IL-6, IL-12, IFN-gamma and GM-CSF concentrations varying over pregnancy. Concentrations may depend on BMI, maternal age and prior preterm delivery.
authors: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ahead@sph.emory.edu
authors: A E
authors: AE
authors: Curry
authors: I
authors: I
authors: Vogel
authors: K
authors: K
authors: Skogstrand
authors: C
authors: C
authors: Drews
authors: D E
authors: DE
authors: Schendel
authors: W D
authors: WD
authors: Flanders
authors: D M
authors: DM
authors: Hougaard
authors: P
authors: P
authors: Thorsen
mesh_terms: D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood* / Q000276:immunology*; D003718:Denmark; D005260:Female; D005865:Gestational Age; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007752:Obstetric Labor, Premature / Q000276:immunology; D011247:Pregnancy / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor