The influence of the mode of delivery on circulating cytokine concentrations in the perinatal period

Malamitsi‐Puchner, Ariadne; Protonotariou, Efthimia; Boutsikou, Τheodora; Makrakis, Evangelos; Sarandakou, Angeliki; Creatsas, George

doi:10.1016/j.earlhumdev.2004.10.017

Cited by 147 publications

(111 citation statements)

References 40 publications

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“…This is consistent with previous findings of a stronger humoral immune response associated with C-section; these children had more IgAand IgG-secreting cells in an ELISPOT assay on PBMCs isolated at 3, 6, and 12 mo of age (12). Similarly, a decreased production of various cytokines, including TNF-a and IL-1b, was observed in blood drawn from Cesarean-delivered newborns compared with cases of vaginal delivery (13). Innate immune recognition of the first microbial stimuli during vaginal delivery is associated with a spontaneous activation of intestinal epithelial cells and subsequent acquisition of TLR tolerance (14).…”

supporting

confidence: 80%

Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice

Hansen

Andersen

Krych

et al. 2014

The Journal of Immunology

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Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also with changes in the immune system. This has further been suggested to link Cesarean section (C-section) with an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section and cross-fostering with a genetically distinct strain influence the gut microbiota composition and immune key markers in mice. Gut microbiota profiling by denaturing gradient gel electrophoresis and 454/FLX-based 16S rRNA gene amplicon sequencing revealed that mice born by C-section had a distinct bacterial profile at weaning characterized by higher abundance of Bacteroides and Lachnospiraceae, and less Rikenellaceae and Ruminococcus. No clustering according to delivery method as determined by principal component analysis of denaturing gradient gel electrophoresis profiles was evident in adult mice. However, the adult C-section–born mice had lower proportions of Foxp3+ regulatory T cells, tolerogenic CD103+ dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates long-term systemic effect on the regulatory immune system that was also evident in NOD mice, a model of type 1 diabetes, born by C-section. However, no effect of delivery mode was seen on diabetes incidence or insulitis development. In conclusion, the first exposure to microorganisms seems to be crucial for the early life gut microbiota and priming of regulatory immune system in mice, and mode of delivery strongly influences this.

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supporting

confidence: 80%

Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice

Hansen

Andersen

Krych

et al. 2014

The Journal of Immunology

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“…The Th1 cytokines stimulate prostaglandins, which are responsible for the commencement of uterine contractions (42). In addition, labor has been found to cause an increase in the neonatal circulation of neutrophils, monocytes, and NK cells; neutrophils and T cells in vaginally delivered infants are activated compared to those in elective caesarean infants (22,33). A surge of cortisol is also associated with labor, and this molecule is immunosuppressive, which may cause the inhibition of both cytokine production and T-cell function in cord blood (33).…”

Section: Discussionmentioning

confidence: 99%

“…During labor, the cytokine environment switches to Th1 to accelerate the inflammatory process which is required for successful labor and delivery. The cytokines that are increased during labor include IL-6, IL-8 (induces cervical ripening), IL-1␤ (stimulates the production of prostaglandin), IL-2, IL-15, IL-18, tumor necrosis factor alpha, and IFN-␥, whereas IL-10 levels are reduced (1,19,22,42). The Th1 cytokines stimulate prostaglandins, which are responsible for the commencement of uterine contractions (42).…”

Section: Discussionmentioning

confidence: 99%

Exposure of Cord Blood toMycobacterium bovisBCG Induces an Innate Response but Not a T-Cell Cytokine Response

Watkins

Semple

Abel

et al. 2008

Clin Vaccine Immunol

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Mycobacterium bovis BCG was introduced as an antituberculosis (anti-TB) vaccine over 80 years ago and has since become one of the most widely used of all vaccines (11,40). Approximately 100 million children worldwide are vaccinated with BCG each year (40). BCG vaccination of infants affords 80% protection against TB meningitis and against disseminated or miliary TB. However, it is variably effective against pulmonary disease at all ages or against the reactivation of latent pulmonary infection in adults (10,37,40). Consequently, in spite of extensive BCG vaccination in many parts of the world, TB rates are high, with about 8 million cases and 2 million deaths annually (32). South Africa ranks eighth in the world for TB incidence, with a rate of approximately 600 cases per 100,000 population (39). Because TB is endemic in South Africa, infants are vaccinated with BCG (Danish strain) shortly after birth. Even with Ͼ95% BCG vaccination coverage, the rate of TB disease in babies remains very high, exceeding 2% per year among children under 2 years old in some areas (13).Little is known about the immune response of human neonates to mycobacteria prior to vaccination with BCG. Ota and coworkers have reported low levels of gamma interferon (IFN-␥), interleukin 5 (IL-5), and IL-13 following the stimulation of cord blood cells with a purified protein derivative of tuberculin (28). Another study that assessed the responses of cord blood to mycobacteria found low levels of secreted IFN-␥, IL-10, and IL-5 following incubation with BCG (16). However, it has not been clear which cells produce these cytokines and how IFN-␥ is induced in the naïve host prior to exposure to mycobacterial antigens and the stimulation of an acquired T-cell response. To further explore the infant immune response prior to vaccination with BCG, we incubated cord blood mononuclear cells (CBMC) and purified CD14 ϩ cells in vitro with the Danish strain of BCG and quantified the IFN-␥, IL-12, IL-10, IL-4, IL-5, and IL-13 secreted into the culture supernatants. Furthermore, to identify the cell types producing these cytokines, intracellular CD4 ϩ and CD8 ϩ T-cell IFN-␥ and IL-10, intracellular CD56ϩ NK cell IFN-␥, and intracellular CD14 ϩ monocyte IFN-␥ and IL-10 were evaluated after the ex vivo incubation of whole cord blood with Danish BCG. The results were compared to the responses of the same cellular subsets in peripheral blood samples from 13-week-old babies vaccinated with BCG at birth. The data indicate that the Th1 cytokine response of the naïve host prior to BCG vaccination was confined to cells of the innate immune system and did not involve T-cell responses. However, post-BCG vaccination, while a similar profile of cytokines was produced, it was T cells that produced IFN-␥, thus providing a larger and more sustainable source of immune stimulation. MATERIALS AND METHODSParticipants. Umbilical cord blood was collected from elective caesarean donors at full term (38 to 39 weeks) to avoid any possible effects of labor. A total

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“…The stress of delivery and environmental changes trigger an inflammatory response even in healthy neonates. 1 The dramatic increase in pro-inflammatory cytokines including tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 is a well documented phenomenon that occurs even in neonates who are born after an uncomplicated pregnancy and delivery. 2,3 Current theories suggest, therefore, that transient elevation of cytokines during the early postnatal phase is a component of normal neonatal adaptation.…”

Section: Introductionmentioning

confidence: 99%

Maternal Cytokine Balance on the Third Postpartum Day is Not Affected by the Mode of Delivery after Healthy Pregnancies

et al. 2010

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Previous reports have suggested that delivery is associated with the induction of inflammatory cytokines. The present study was designed to investigate whether increased cytokine production was present on postpartum day 3 after a normal pregnancy and whether any changes were associated with the mode of delivery. In total, 33 pregnant women were enrolled; 18 delivered vaginally and 15 underwent an elective caesarean section (C-section). The levels of 17 cytokines and growth hormones were measured at the beginning of delivery or before anaesthesia and on postpartum day 3.While interleukin (IL)-6 and IL-8 levels decreased significantly postpartum, other cytokine concentrations were comparable before and after delivery. Only IL-7 levels were significantly increased in the Csection patients compared with the vaginal birth patients postpartum. In conclusion, there was no risk of a prolonged maternal inflammatory reaction after an uncomplicated vaginal birth or elective C-section, so it is probably not necessary to consider this as an issue when making a decision on the mode of delivery following uncomplicated pregnancy.

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The influence of the mode of delivery on circulating cytokine concentrations in the perinatal period

Cited by 147 publications

References 40 publications

Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice

Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice

Exposure of Cord Blood toMycobacterium bovisBCG Induces an Innate Response but Not a T-Cell Cytokine Response

Maternal Cytokine Balance on the Third Postpartum Day is Not Affected by the Mode of Delivery after Healthy Pregnancies

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