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The Journal of Immunology, 2009, 182, 3285 -3293
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0711996

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Th1/Th2 Patterns and Balance in Cytokine Production in the Parents and Infants of a Large Birth Cohort1

Marilyn Halonen2,*,{ddagger},§, I. Carla Lohman{ddagger}, Debra A. Stern{ddagger}, Amber Spangenberg{ddagger}, Dayna Anderson{ddagger}, Sara Mobley{ddagger}, Kathy Ciano{ddagger}, Michael Peck{ddagger} and Anne L. Wright{dagger},{ddagger}

* Department of Pharmacology and {dagger} Department of Pediatrics, {ddagger} Arizona Respiratory Center, College of Medicine and § Bio5 Institute, University of Arizona, Tucson, AZ 85724

Regulation of human immune cell cytokine production in vivo is not well understood due in part to limitations on imposing experimental conditions. We proposed that life-imposed conditions (pregnancy, birth, age, gender), combined with large sample size, repeat sampling, and family-based recruitment would serve to reveal peripheral blood cell-derived cytokine patterns reflective of in vivo regulation regarding Th1/Th2 balance and familial correlation. Mononuclear cells were obtained from 483 trios in the Tucson Infant Immune Study: from mothers pre- and postpartum, infants at birth and at 3 mo, and fathers. Con A/PMA-stimulated supernatants were assayed by ELISA for IFN-{gamma}, IL-4, IL-13, IL-5, and IL-10 and allergen-stimulated supernatants for IFN-{gamma}, IL-4, and IL-13. Mitogen-stimulated prepartum samples were not globally Th2 biased, differing from postpartum only by a modestly reduced IFN-{gamma}:IL-5 ratio. Prepartum samples actually produced less IL-10 and IL-13 although more IL-5 than paternal samples. Newborns were also not globally Th2 biased, with mitogen stimulation producing ~10-fold less IL-4, IL-5, and IFN-{gamma} than adults but only 2- to 3-fold less IL-13 and IL-10. Despite these group differences, all cytokines showed marked positive intraindividual correlations (all p < 0.001). Allergen stimulation gave results consistent with a lack of global Th2 bias. Mitogen stimulation revealed parent-child and parent-parent correlations. Thus, rather than a global Th2 bias, cytokine production in pregnant mothers and newborns appears regulated so as to maintain a relative balance among the cytokines, with the nature of the balance differing in mothers and infants and with production influenced by familial factors that include shared environment.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was funded in part by National Institutes of Health Grants AI 42268, AI 61811, and HL67672.

2 Address correspondence and reprint requests to Dr. Marilyn Halonen, Arizona Respiratory Center, University of Arizona HSC, Tucson, AZ 85724. E-mail address: mhalonen{at}arc.arizona.edu

3 Abbreviations used in this paper: CBMC, cord blood mononuclear cell; LSM, lymphocyte separation medium.

4 The online version of this article contains supplemental material.




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