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      Neuroimmune-Endocrine Interactions during Early Pregnancy in an Autoimmune Context: Focus on Macrophage Activation

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          Abstract

          Neuroimmune-endocrine interactions seem to be central to the dialogue between the mother and the growing embryo during normal pregnancy. A proinflammatory Th1 microenvironment appears to be associated with embryo implantation but an excess of these cytokines may be deleterious. When normal gestation is subjected to stressful stimuli as those provided by a chronic inflammatory milieu, the activation profile of T cells and macrophages may be temporarily changed. Although much evidence supports the protective role of pregnancy in Th1 autoimmune diseases, the comprehension of the maternofetal interaction in an inflammatory context may serve to get more insight into pregnancy failures. Macrophages integrate multiple inputs and signals of neuroimmune-endocrine systems and they appear as major participants in either embryo implantation or loss. Changes at the macrophage level during gestation might help to understand their regulatory role in embryo implantation as well as to disclose their local and systemic pathogenic potential.

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          Most cited references38

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          Innate and adaptive immunity in female genital tract: cellular responses and interactions.

          The mucosal immune system in the female reproductive tract (FRT) has evolved to meet the unique requirements of dealing with sexually transmitted bacterial and viral pathogens, allogeneic spermatozoa, and the immunologically distinct fetus. Analysis of the FRT indicates that the key cells of the innate and adaptive immune systems are present and functionally responsive to antigens. Acting through Toll-like receptors in the Fallopian tubes, uterus, cervix, and in the vagina, epithelial cells, macrophages, natural killer cells, and neutrophils confer protection through the production of chemokines and cytokines, which recruit and activate immune cells, as well as bactericidal and virucidal agents, which confer protection at times when adaptive immunity is downregulated by sex hormones to meet the constraints of procreation. The overall goal of this paper is to define the innate immune system in the FRT and, where possible, to define the regulatory influences that occur during the menstrual cycle that contribute to protection from and susceptibility to potential pathogens. By understanding the nature of this protection and the ways in which innate and adaptive immunity interact, these studies provide the opportunity to contribute to the foundation of information essential for ensuring reproductive health.
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            Th1-type immunity is incompatible with successful pregnancy.

            Several years ago, the rather provocative question was raised: is successful pregnancy a T helper 2 (Th2) phenomenon? Implicit in this argument is the corollary that unsuccessful pregnancy is a Th1-type situation. Here, evidence from murine and human pregnancy is presented to show that, since Th1-type cytokines mediate pregnancy loss, a shift towards Th1-type immunity may help resolve 'unexplained' pregnancy failure.
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              Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF.

              We aimed to study T-helper 1 (Th1) and Th2 intracellular cytokine expression in peripheral blood lymphocytes of women with recurrent spontaneous abortions (RSA) or infertility with multiple implantation failures after IVF cycles. Twenty-six women with three or more RSA and 23 with two or more IVF failures (14 with no history of spontaneous abortion (SAB) and nine with more than one SAB) comprised the two study groups. Twenty-one non-pregnant healthy multiparous women served as controls. Proportions (%) of lymphocytes containing IFN-gamma, TNF-alpha, IL-4 and IL-10 and the Th1/Th2 ratios of IFN-gamma/IL-4, IFN-gamma/IL-10, TNF-alpha/IL-4 and TNF-alpha/IL-10 in CD3+, CD3+/CD8- (T helper) and CD3+/CD8+ (T suppressor) cells were measured by 4-colour flow cytometry. RSA women demonstrated significantly higher Th1/Th2 ratios of IFN-gamma/IL-4 (P < 0.01), TNF-alpha/IL-4 and TNF-alpha/IL-10 (P < 0.05 each) in CD3+/CD8- T helper cells than those of controls. The proportion of TNF-alpha producing CD3+/CD8- cells (P < 0.05), and the Th1/Th2 ratios of TNF-alpha/IL-4 (P < 0.05) and TNF-alpha/IL-10 (P < 0.005) in CD3+/CD8- cells were significantly higher in women with multiple IVF failures without SAB as compared with those of controls. The prevalence of dominant Th1 immune responses in peripheral blood lymphocytes may reflect the systemic contribution of Th1 cytokines to RSA or multiple implantation failures in IVF cycles.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                978-3-8055-8608-5
                978-3-8055-8609-2
                1021-7401
                1423-0216
                2008
                July 2008
                29 July 2008
                : 15
                : 1
                : 84-90
                Affiliations
                aDepartamento de Química Biológica, Facultad de Ciencias Exactas y Naturales y bCentro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina
                Article
                135628 Neuroimmunomodulation 2008;15:84–90
                10.1159/000135628
                18667804
                d6a8bf79-2b41-413a-bd88-14dfbb78cf47
                © 2008 S. Karger AG, Basel

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                History
                Page count
                Tables: 1, References: 51, Pages: 7
                Categories
                Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Autoimmune diseases, chronic,Pregnancy,Macrophages,Neuroimmune regulation

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