Changes in ovine maternal temperature, and serum cortisol and interleukin-6 concentrations after challenge with Escherichia coli lipopolysaccharide during pregnancy and early lactation1

Abstract

Major changes in maternal physiology during pregnancy and lactation can have a large impact on the immune and neuroendocrine systems. One of the most significant changes, observed in rats and mice, is hyporesponsiveness of the hypothalamic pituitary adrenal axis (HPAA) in response to inflammation, restraint, and other psychological stressors during late pregnancy and lactation. This attenuation, however, has not been well characterized in ruminant animals and may be relevant to their susceptibility to inflammatory diseases during these periods. Thus, the intent of this study was to characterize responsiveness of the ovine HPAA to inflammatory challenge during pregnancy and lactation. Ewes from early (33 d), middle (55 d), and late (138 d) pregnancy, as well as early lactation (10 d), were challenged i.v. with a bolus dose of 400 ng of Escherichia coli lipopolysaccharide (LPS)/kg of BW or saline. A corresponding group of nonpregnant ewes was also challenged with LPS to serve as positive control animals for each pregnancy and lactation study. Responsiveness of the HPAA was assessed by measuring the 4-h change in serum cortisol concentration after LPS challenge. The cortisol increase after LPS challenge was elevated (P < 0.01) in pregnant ewes during late pregnancy over that of nonpregnant animals. In contrast, the characteristic temperature response associated with systemic LPS challenge was decreased (P < 0.01) during early pregnancy and lactation compared with nonpregnant or nonlactating animals. Serum IL-6 concentrations were measured to assess whether changes in HPAA responsiveness during pregnancy or lactation were attributed to changes in proinflammatory signaling to the HPAA. Interestingly, enhanced cortisol responsiveness during late pregnancy was correlated with increased (P < 0.01) serum IL-6 concentrations, indicating that IL-6 may contribute to enhanced HPAA responsiveness during this period. Serum IL-6 concentrations during early and midpregnancy did not increase in response to LPS challenge, indicating that HPAA activation during periods of pregnancy may be independent of IL-6 production.

Effects of dietary fish meal and soybean meal on the ovine innate and acquired immune response during pregnancy and lactation

“…First, it is possible that the LPS challenge dose used in the present study was too high to detect subtle changes in neuroendocrine function in sheep, as we have historically used a challenge dose of 400 ng/kg as opposed to 1.2 g/kg to assess their neuroendocrine function (Kabaroff, 2006a); the rationale for choosing this LPS dose was that it had to induce fetal stress in order to examine the protective effects of FM supplementation on fetal programming, and a previous study performed by our group demonstrated that this dose induced fetal stress and affected programming of the ovine hypothalamic-pituitaryadrenal axis . Second, it has been previously demonstrated that sheep are hyperadrenal cortisol responsive to LPS during this stage of pregnancy, possibly due to fetal cortisol secretion (Kabaroff et al, 2006b). Given this, it is also possible that FM supplementation was not sufficient to attenuate the combined effects of maternal and fetal ACTH and cortisol secretion.…”

Hormonal Profiles of Late Gestation Ewes Following Intra-uterine Inoculation With and Without Lux-modified Escherichia coli

“…with Streptococcus pyogenes peptidoglycan on d 5 after mating, increased concentrations of cortisol in a biphasic pattern were observed [21]; although in the low dose S. pyogenes peptidoglycan group pregnancy was maintained even though fever was induced and concentrations of cortisol were elevated [21]. An increase in concentrations of cortisol as a result of immune system interactions (direct and/or indirect) in concert with physiological stress to the animal is a typical response; as has been observed previously during pregnancy toxemia in the ewe [12] and following LPS exposure in the pregnant ewe [13] and fetus of the pregnant ewe [22]. Again, it is not clear why serum concentrations of cortisol differed between bacterial-inoculated ewes and Controls in Experiment 1 but not in Experiment 2.…”

“…However we cannot rule out that placement of the inoculum, E. coli serovar, plasmid effects or that a combination did not influence the progression of infection and induction of a differential immune response between the two studies. As an elevation in serum concentrations of cortisol in response to an infection of the type reported here is characteristic (see Experiment 1 in this study, and refs [12,13,21,22]), this requires further study.…”

“…While endogenous cortisol increases fetal glycogenesis when secreted during late pregnancy, and increases as part of the normal signaling prior to parturition [11], stimulation of the immune system and physiological stress during pregnancy toxemia [12] or in response to i.v. E. coli LPS challenge [13] in the pregnant ewe can also increase cortisol; which may have negative consequences to pregnancy maintenance in response to infection. Nevertheless, the effects of intrauterine inoculation on endocrine parameters of the ewe as a possible model for bacterial abortion in ruminant animals have not been fully evaluated.…”

Effect of salsolinol on ACTH and cortisol response to handling stress in early anestrous sheep

“…Further, studies on lactating rats revealed elevated basal secretion of adrenocorticotropic hormone (ACTH) and corticosterone, with a flattened diurnal rhythm for corticosterone secretion (Windle et al 2013). However, no changes in basal cortisol secretion have been observed in lactating sheep (Kabaroff et al 2006;Tilbrook et al 2006).…”