Lymphocyte responses to stress in postpartum women: relationship to vagal tone
Introduction
In females, naturally occurring conditions including the menstrual cycle, pregnancy, lactation, and menopause are associated with changes in multiple hormonal and physiological systems that modulate immune function. For example, glucocorticoid secretion, which increases in late pregnancy and declines dramatically at the time of parturition, reportedly affects immune system activity (Sternberg, 1995). Lymphocyte glucocorticoid receptor mRNA expression is reduced in the luteal phase of the menstrual cycle (Altemus et al., 1997). Estrogen, which varies as a function of the menstrual cycle, gestation and breastfeeding, influences inflammatory cell adhesion molecules (Koh et al., 1997), tumor necrotic factor, and interleukin-6 (Zuckerman et al., 1996).
Postmenopausal estrogen and progesterone hormone replacement can influence vagal activity and concomitantly increase lymphocyte responses to mitogen and was associated with an attenuated response to a laboratory stressor (Burleson et al., 1998). Prolactin, which is elevated during pregnancy and lactation, can increase mitogen-stimulated splenocyte and thymocyte activity (Postel-Vinay et al., 1997) and elevated prolactin is associated with increased titers of auto-antibodies (Neidhart, 1996). It has also been suggested that oxytocin, which is secreted during pregnancy and lactation, may modulate immune function (Rivest and Laflamme, 1995).
Acute psychological stress also is known to produce changes in immune responses in humans. Following a variety of acute stressors reductions were found in lymphocyte proliferation to mitogens including phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) (e.g. Bachen et al., 1992, Brosschot et al., 1992, Sieber et al., 1992, Redwine et al., 1996a). In recent years many studies in both men and women have shown that sympathetic activity, via adrenergic mechanisms, mediates at least some of the effects of acute psychological stress on cellular immune function (e.g. Madden and Felten, 1995, Benschop et al., 1996). In men following exposure to a psychological stressor the density of beta-adrenergic receptors on lymphocytes increased; this increase was associated with a decrease in lymphocyte proliferation (Redwine et al., 1996a). Manuck et al. (1992) and Bachen et al. (1992) found that individuals with high levels of cardiovascular and/or catecholaminergic reactivity had greater immune changes to stress. Fewer studies have looked at parasympathetic influences, which may attenuate the effects of sympathetic activity associated with stress (e.g. Burleson et al., 1998). In addition, few studies have examined immune responses to stress in women as a function of events associated with reproduction (Herbert et al., 1994, Caggiula et al., 1995, Mills et al., 1995, Burleson et al., 1998).
There is growing evidence that hormone responses to stressors are attenuated in lactating rats and humans (reviewed Carter and Altemus, 1997, Uvnäs-Moberg, 1998). Following intense exercise, lactating women showed less increase in ACTH and cortisol when compared to postpartum women who were bottlefeeding their infants; pre-stress levels of these hormones were similar in both groups (Altemus et al., 1995). A reduced catecholamine response to immobilization was found in lactating compared with non-lactating female rats (Higuchi et al., 1989). Intraperitoneal injections of saline produced increases in corticosterone, gene expression for CRF and enkephalin in non-lactating, but not in lactating rats (Lightman and Young, 1989). The finding that stress-related neuroendocrine activity is attenuated in lactating/postpartum women suggests that corresponding immune changes also might be blunted.
A few studies have reported changes in immune activity during the postpartum period. Changes in proportions of circulating immune cell sub-populations in postpartum women can be detected for at least a year following childbirth (Watanabe et al., 1997). Lactation has been associated with increased lymphocyte proliferation to the mitogen, Conconavaline A in rats (Redwine et al., 1996b). However, whether immune responses to stress are altered during the postpartum period has not been investigated. The goal of the present study was to determine the effect of postpartum status on lymphocyte proliferation responses to mitogens at baseline and following an acute psychological stress task (public speaking and mental arithmetic). Because studies found that lactation was associated with changes in immune and endocrine activity we compared women who were exclusively breastfeeding to women who had recently given birth but who elected to bottlefeed their infants. In addition, comparable women who were not pregnant and who had not given birth for at least three years also were studied. Since autonomic and stress hormone responses are known to affect lymphocyte proliferation responses to stress, we also measured pituitary-adrenal hormones and autonomic responses to stress.
Section snippets
Methods
Two groups of postpartum women were studied, those who were breastfeeding (n=16) and those who had elected to bottlefeed (n=10). Additionally, non-postpartum controls (n=10) were examined who had not given birth within the last three years and were tested during the follicular phase of their menstrual cycle (within 7 days of the onset of their last menstrual period). Breastfeeding and bottlefeeding subjects were tested between 6 and 18 weeks postpartum. The average (±SEM) number of weeks
Results
Across breastfeeding, bottlefeeding and non-postpartum groups physiological measures were taken as a function of an acute exposure to a challenging speech and mental arithmetic task (Table 1. Immune proliferation responses to stress differed between the groups for PWM. There was a time effect [(F=5.8, P<0.01)], no group effect [(F=1.5, P=0.25)] and a group by time interaction for lymphocyte proliferation to PWM [F=2.26, P<0.05]. Post hoc comparisons showed that exposure to the psychological
Discussion
The results of this study indicate that lymphocyte activity in response to a psychological stressor can vary as a function of a woman's postpartum status. The decrease in lymphocyte proliferation to PWM stimulation in the non-postpartum women following stress did not occur in the postpartum women, suggesting that lymphocyte responses in both breastfeeding and bottlefeeding women are sometimes less reactive. Although, a stress response was not found in any of the groups for lymphocyte
Acknowledgements
This work was performed in the National Institute of Mental Health (NIMH) Intramural Research Program. This work was also partially supported by Department of Defense Women's Health Program Grant # DAMD17-95-1-5069, NIMH K05-MH 01050 to C.S.C. and NIMH T32 18399.
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