Lactation alters the effects of conditioned stress on immune function

Abstract

During lactation, endocrine function is altered and stress responses are dampened. Stress effects on immune function are partially determined by endocrine factors; therefore, we assessed whether stress similarly alters immune function during lactation. Sprague-Dawley rats were conditioned by exposure to a tone paired with foot shock (2 sessions, 16 shocks each) prior to breeding or were left undisturbed. Lactating (day 10) (Lac) and nonlactating diestrous virgin controls (C) were killed immediately after reexposure to the tone or removal from their home cage. Plasma corticosterone stress responses were dampened in Lac relative to C animals. Peripheral blood lymphocyte proliferation to T cell receptor antibody stimulation was reduced to a similar extent in both experimental groups. Conditioned stress reduced splenocyte proliferation and increased nitrite accumulation in C animals, but not in Lac animals. Mesenteric lymph node lymphocyte proliferation was significantly increased after stress in Lac compared with C animals. Both plasma interleukin-6 (IL-6) and phytohemagglutinin-stimulated splenic IL-6 production were increased in Lac animals compared with C animals after stress exposure. These data indicate that stress-induced alterations may be determined by different regulatory mechanisms within immune compartments and that these effects depend on the physiological state of the organism.

Effects of reproductive status on behavioral and endocrine responses to acute stress in a biparental rodent, the California mouse (Peromyscus californicus)

“…No differences were found in the magnitude of the CORT response to stress among breeding, nonbreeding, and virgin females. These results contrast with numerous findings in rats, in which lactating dams were shown to have a reduced CORT response to noise, endotoxin, elevated plus maze, and light/dark box tests compared to virgin females (Lightman, 1992; Shanks et al, 1997; Toufexis et al, 1999b; Windle et al, 1997a). Again, our findings might reflect the fact that the breeding females in the present study were concurrently pregnant and lactating, unlike the lactating females used in previous studies of other rodent species.…”

“…Lactational hyporesponsiveness, or blunted responsiveness to stress in lactating females, has been described in a number of mammalian species, including sheep ( Ovis aries ), flying foxes ( Pteropus hypomelanus ), Columbian ground squirrels ( Spermophilus columbianus ), Norway rats ( Rattus norvegicus ), and humans (Deschamps et al, 2003; Hubbs et al, 2000; Lightman, 1992; Reeder et al, 2004; Shanks et al, 1997; Tilbrook et al, 2006; Tu et al, 2005; Windle et al, 1997a). This phenomenon has been characterized most thoroughly in rats.…”

“…This phenomenon has been characterized most thoroughly in rats. Compared to virgin females, lactating female rats have been found to exhibit reduced adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses to a variety of stressors, including immobilization, endotoxins, acoustic startle, predator urine, and open-field tests (Deschamps et al, 2003; Lightman, 1992; Shanks et al, 1997; Toufexis et al, 1999a; Windle et al, 1997a). Lactating rats also exhibit reduced anxiety-like and stress-related behavior in open-field, elevated plus maze, noise stress, and acoustic startle response tests, compared to virgin females (Fleming and Luebke, 1981; Lonstein, 2005; Toufexis et al, 1999b; Windle et al, 1997a).…”

Adaptive Changes in Basal and Stress-Induced HPA Activity in Lactating and Post-Lactating Female Rats

“…Early studies by Levine and colleagues showed that responses to footshock and ether stress were reduced in lactating rats (16, 17), and subsequent studies have shown attenuated responses to a wide variety of stresses. These include both psychological stresses—such as noise stress (18), conditioned footshock (19), forced swimming (20–22), and restraint (23, 24)—and physical stresses, such as intraperitoneal injection of NaCl (25) or lipopolysaccharide (26), or exposure to ether vapor (23). While this stress hyporesponsiveness is consistent in rodents, the situation is less clear in primates (15).…”

Hormonal influences on neuroimmune responses in the CNS of females

“…Suppressed responses to stress in pregnancy can be explained by adaptations in both the anterior pituitary and the hypothalamus (Brunton et al, 2005; Russell et al, 2008). Corticotrophs in the pituitary are less sensitive to secretagogs (Shanks et al, 1997; Neumann et al, 1998), and CRH mRNA expression induced by stress is attenuated (Brunton et al, 2005). Moreover, HPA axis responses to immune stress in early mid pregnancy are strong and similar to that in virgins, although activation of hypothalamic vasopressin neurons, rather than CRH neurons, may be more important in the stress response in pregnancy (Ma et al, 2005; Parker et al, 2011).…”