Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort.
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 approximately 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.
Halonen
Marilyn
M
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. mhalonen@arc.arizona.edu
Lohman
I Carla
IC
Stern
Debra A
DA
Spangenberg
Amber
A
Anderson
Dayna
D
Mobley
Sara
S
Ciano
Kathy
K
Peck
Michael
M
Wright
Anne L
AL
D000328:Adult; D000485:Allergens / Q000502:physiology; D001249:Asthma / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010290:Parents; D011247:Pregnancy; D011446:Prospective Studies; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D012307:Risk Factors; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D016207:Cytokines