In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory?

• Published in: PloS one Vol. 12; no. 6; p. e0177813
• Main Authors: Graham, Caroline, Chooniedass, Rishma, Stefura, William P, Becker, Allan B, Sears, Malcolm R, Turvey, Stuart E, Mandhane, Piush J, Subbarao, Padmaja, HayGlass, Kent T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.06.2017; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Age; Anti-Inflammatory Agents - immunology; Anti-Inflammatory Agents - metabolism; Asthma; Babies; Bias; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Birth; Canada; Chemokines; Childbirth & labor; Children & youth; Childrens health; Correlation analysis; CXCL10 protein; Cytokines; Female; Fetuses; Genetic aspects; Gestational Age; Health risk assessment; Humans; Immune response; Immune status; Immunity; Immunity, Innate - immunology; Immunology; In vivo methods and tests; Infants; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Innate immunity; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 10; Interleukin 18; Kinetics; Longitudinal Studies; Medicine and Health Sciences; Monocyte chemoattractant protein 1; Pediatrics; Physiological aspects; Postpartum; Preeclampsia; Pregnancy; Pregnant women; Proteins; Signatures; Studies; Tumor necrosis factor; Womens health; Young Adult; Canada; Manitoba Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0177813

Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20-57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50-100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy.