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Biomedical subjects

C L Coe

Publications and source records attributed to C L Coe.

At least 19 recordsLinked to original sources

Effects of early rearing environment on immune responses of infant rhesus monkeys.

In animals, perturbations of the rearing environment have been shown to alter behavior, cognition, and physiology, including immune responses. In order to evaluate the effect of early rearing conditions on the development of immune responses in the infant primate, several immunological measures were assessed in rhesus monkey infants, nursery-reared (NR) or mother-reared (MR), from birth to 2 years of age. Rearing in the absence of the mother affected several aspects of cellular immunity. NR monkeys had significantly lower proportions of CD8 cells and lower natural killer cell activity than did MR monkeys. In contrast, their lymphocyte proliferation responses to mitogen stimulation were higher than those of MR monkeys. An attempt to behaviorally rehabilitate the NR infants at 1 year of age did not result in a recovery of normal immune responses. This study indicates that abnormal early rearing may have long-lasting effects on the immune system, which could have health consequences later in life.

Animal Husbandry

Bidirectional effects of interleukin-1 on immune responses in rhesus monkeys.

Physiological and pharmacological doses of recombinant human interleukin-1 (IL-1) were administered intravenously to juvenile rhesus monkeys in order to evaluate its effects on immune and endocrine activity. Mitogen-induced lymphocyte proliferation was increased following 1-ng and 1-microgram doses of IL-1, but decreased following 10- and 50-micrograms doses. Natural killer cell cytotoxicity was also significantly reduced at the 10-micrograms dose and tended to be below baseline at the 50-micrograms dose. These changes were associated with marked neutrophilia observed after administration of IL-1. These results indicate that peripheral administration of IL-1 can either enhance or inhibit the numbers and responses of immune cells in rhesus monkeys depending on the dose administered. These responses may have been the result of differential activation of the endocrine system, because levels of pituitary hormones in plasma increased progressively with increasing doses of IL-1. Thus, the extent to which a particular dose of IL-1 induces the release of pituitary-adrenal hormones may be related to the direction and magnitude of the resulting changes in immune activity.

Adrenocorticotropic Hormone

Temporal and social factors influencing behavioral and hormonal responses to separation in mother and infant squirrel monkeys.

The behavioral and hormonal responses of mother and infant squirrel monkeys (Saimiri sciureus) were examined to assess temporal and environmental factors that influence the response to separation. In two experiments evaluating the effects of 1-, 3-, 6-, and 24-hr separations, it was found that signs of infant behavioral agitation decreased over time, whereas adrenocortical activation persisted or even increased. Moreover, two separation environments were shown to differentially affect behavioral and hormonal responses. Separated infants vocalized significantly more when their mothers were proximal than when isolated, but showed lower cortisol levels in the adjacent separation than in the total-isolation condition. These data indicate that the intensity of the infant's calling response cannot be used to predict internal state (as reflected by cortisol levels). Furthermore, vocalization rate is highly dependent upon contingent stimuli, such as the presence of maternal cues. Following separation, the mothers also showed elevated cortisol levels. However, both the magnitude and pattern of the response differed considerably from that of the infant.

Animals

Self-discrepancy and natural killer cell activity: immunological consequences of negative self-evaluation.

The study tested whether self-discrepancy theory could account for changes in natural killer (NK) cell activity after exposure to self-referential stimuli. Anxious, dysphoric, and control Ss were pretested and 1 month later covertly exposed to their own self-guides as well as those of another S. Blood samples were drawn for analysis of NK cytotoxicity and cortisol. The dysphoric Ss manifested the greatest actual:ideal discrepancy, whereas the anxious Ss manifested the greatest actual:ought discrepancy. Content analysis of written responses showed that activating discrepancies induced specific negative states; priming discrepancies also increased cortisol for the anxious Ss. NK activity was lower after self-referential priming for both distressed groups, particularly the anxious Ss. The control Ss showed a trend toward increased NK activity after self-referential priming. The study represents the 1st experimental demonstration that negative self-evaluation can alter immune responses.

Adult

Vulnerability of placental antibody transfer and fetal complement synthesis to disturbance of the pregnant monkey.

Maternal and fetal/infant antibody levels were assessed across pregnancy and at birth to evaluate the prenatal transmission of IgG in the rhesus monkey. Although some antibody was evident in the fetus by midpregnancy, the marked increase in IgG occurred primarily during the last two weeks of pregnancy. This delay until the end of pregnancy would result in low antibody titers in premature infants. In contrast, when gestation length was normal, the placental transfer of IgG was resistant to both dexamethasone treatment and a prolonged period of stress during pregnancy. This resiliency occurred despite an effect of prenatal stress on other aspects of infant development, including physical growth and the fetal synthesis of complement proteins.

Animals

Repeated social stress during pregnancy impairs neuromotor development of the primate infant.

Neuromotor responses were assessed in 90 infant squirrel monkeys born from normal and stressed pregnancies. Repeated psychological disturbance during pregnancy, evoked by disruption of the pregnant female's social relationships, significantly altered the performance of the young infant on a standardized battery of neuromotor tests. As compared with infants from undisturbed pregnancies, infants from chronically stressed pregnancies had poorer motor abilities, impaired balance reactions, and reduced postrotary nystagmus. They also had shorter attention spans and looking episodes during the administration of orientation items. In contrast, when only a single stressful period was imposed during midgestation, infants were not significantly different from control subjects. These findings indicate that sustained stress across pregnancy can have deleterious effects on fetal development, but a short period of stress, at least when restricted to midgestation, does not appear to adversely affect neuromotor responses of the young primate infant.

Animals

Psychosocial factors and immune senescence in the aged primate.

With increasing age, old animals and humans show decreases in a number of immune responses indicative of the process of immune senescence. Our studies investigated whether social companionship, as a potentially positive psychological intervention, would increase lymphocyte proliferation and natural killer cell activity in the aged nonhuman primate. Contrary to our initial hypothesis, social stimulation resulted in decreased immune responses in old monkeys. With specific modifications of the housing conditions it was possible to prevent these decreases in immune responses from occurring, but social companionship still failed to enhance immune responses in the aged monkey.

Aging

Endocrine activation mimics the adverse effects of prenatal stress on the neuromotor development of the infant primate.

Pregnant female rhesus monkeys were exposed to a 2-week period of adrenocorticotropic hormone (ACTH) to determine whether it would affect the early neuromotor development of their fetuses in a manner similar to that observed after psychological stressors. During the first month after birth, infants were tested on two occasions with a modification of the Brazelton Newborn Behavioral Assessment Scale. Infants derived from ACTH-treated pregnancies showed early impairments in motor coordination and muscle tonicity and shorter attention spans as compared to controls. In addition, on a temperament rating scale, infants from the ACTH condition were more irritable and difficult to console. These findings indicate that a delimited period of endocrine activation during pregnancy can have an adverse effect on infant neurobehavioral development, like that of prenatal stress.

Adrenocorticotropic Hormone

Maternal influences on body temperature in the infant primate.

The following study investigated the diurnal variation in body temperature of the young monkey infant and assessed the role that the mother plays in the development of the temperature rhythm. Using an implantable biotelemetry system, core body temperature and motoric activity were evaluated in maternally-reared and hand-reared rhesus monkey infants across the first several months of life. Our results indicated that the nocturnal temperatures of hand-reared infants are lower than those of mother-reared infants at one month of age, and that there are persistent differences in the orientation and shape of the diurnal temperature rhythm. The initial thermal challenge and the prolonged rhythm shift may have implications for the normal development of several physiological systems in the hand-reared infant monkey.

Animals

Early rearing conditions alter immune responses in the developing infant primate.

The influence of early rearing conditions on immunologic development was investigated in infant monkeys. Lymphocyte proliferation, natural killer cell activity, and antibody responses to tetanus vaccination were compared in 30 rhesus monkeys reared under five different conditions. Lymphocyte responses to two mitogens (concanavalin A and pokeweed) were significantly increased in infants from disturbed rearing conditions compared with control infants that had been reared in an undisturbed manner by their mothers. The largest increases occurred in nursery-reared monkeys that had been fed Similac infant formula. The nursery-reared monkeys also tended to show lower natural killer cell activity, but there were no significant differences in response to vaccination. These findings support other research indicating that psychologic and nutritional aspects of the early rearing environment may have long-lasting effects on some, but not all, immune responses in the developing infant.

Animal Husbandry

Time-dependent effects of peer separation on lymphocyte proliferation responses in juvenile squirrel monkeys.

This study evaluated the immunological, hormonal, and behavioral responses of juvenile squirrel monkeys to repeated social separations of varying length. Following a 3-hr separation, lymphocyte responses to stimulation with the mitogen concanavalin A (Con A) declined significantly, and these alterations were sustained after a 24-hr separation period. The responses to Con A and to a second mitogen, phytohemagglutinin (PHA), were suppressed after 2 days. At the end of a 7-day separation period, immune responses were not significantly different from basal values. Plasma cortisol levels were elevated above basal levels in all animals after the 3-hr, 24-hr, and 2-day separations, but were not elevated after the 7-day separation. While we observed no statistically significant changes in locomotor activity or calling behavior during any of the separations, the monkeys tended to be most active and to call most immediately following separation. Our findings concur with earlier reports indicating that social stressors can influence lymphocyte proliferation in nonhuman primates and that certain cell types might be differentially sensitive to stress, but also indicate that these influences are transient.

Animals

Frontal brain asymmetry and immune function.

The relation between brain activity and the immune system was evaluated by assessing immune responses in 20 healthy women who manifested extreme differences in the asymmetry of frontal cortex activation. One group showed extreme and stable left frontal activation; the other group showed extreme and stable right frontal activation. As predicted, women with extreme right frontal activation had significantly lower levels of natural killer cell activity (at effector:target cell ratios of 33:1 and 11:1) than did left frontally activated individuals. This difference did not extend to two other immune measures, lymphocyte proliferation and T-cell subsets. However, higher immunoglobulin levels of the M class were observed in the right frontal group. In this study, the immune patterns could not be accounted for by plasma cortisol levels, anxiety- and depression-related symptomatology, or recent health histories. These findings support the hypothesis that there is a specific association between frontal brain asymmetry and certain immune responses.

Adolescent

Influence of early rearing on lymphocyte proliferation responses in juvenile rhesus monkeys.

Lymphocyte proliferation responses and natural killer cell activity were evaluated in 35 juvenile rhesus monkeys derived from five different rearing conditions. Nursery-reared monkeys had proliferation responses which were significantly higher than those of mother-reared subjects. Reexamination of the nursery-reared monkeys 1.5 years later indicated that an abnormally high response to concanavalin A was still evident at 2.5 years of age, but both PHA and PWM responses had shown an age-appropriate decrease into the normal range for this species. Proliferation responses in monkeys that had been weaned early from their mothers at 6 months of age were also higher than values for control monkeys that remained with their mothers, but below those of the nursery-reared monkeys. In contrast, monkeys that had received multiple separations from the mother between 3 and 7 months of age showed lymphocyte proliferation responses that were below normal. These results indicate that early rearing conditions can have a lasting effect on certain immune responses in the developing primate.

Aging

Effects of age, sex, and psychological disturbance on immunoglobulin levels in the squirrel monkey.

The following research assessed the influence of developmental, hormonal, and psychological factors on immunoglobulin and complement protein levels in the squirrel monkey. A cross-sectional life span study established that the developmental pattern of immunoglobulins and complement proteins was similar to that observed in humans. IgG and IgM levels rose progressively with age, while the complement system was mature at birth. In contrast to humans, this species showed a significant sex difference in IgG levels, with higher levels in males during both infancy and adulthood. Males also showed a greater antibody response to viral challenge than did females, and evaluation of gonadectomized subjects suggested that the sex difference in antibody production was testosterone-dependent. The effect of acute and sustained psychological disturbance on IgG levels was also evaluated in infant monkeys. Repeated, brief separations from the mother did not alter IgG levels, but IgG levels were suppressed after a 7-day removal from the mother. Therefore, despite the general view that immunoglobulin levels are relatively stable, these studies have established that immunoglobulin levels can be strongly influenced by hormonal and experiential factors in the squirrel monkey.

Aging

Prolonged effect of psychological disturbance on macrophage chemiluminescence in the squirrel monkey.

The following study assessed changes in macrophage responsiveness after a 24-h period of psychological disturbance in mother and infant squirrel monkeys. Utilizing a luminol-dependent assay, an 80-min chemiluminescent burst was measured in blood monocytes in response to zymosan stimulation. Cells obtained from stressed mothers and infants showed significant increases in chemiluminescence (CL) as compared to baseline levels. Moreover, the elevated pattern of response persisted for at least 2 weeks after the mothers and infants were reunited. The initial change in CL was associated with increased pituitary-adrenal activity and leukocyte redistribution, but these measures returned to normal levels following reunion. Thus, this study has demonstrated a prolonged change in an immune parameter following a transient alteration in the psycho-endocrine status of the host.

Animals

Aging and immunity in non-human primates. II. Lymphocyte response in thymosin treated middle-aged monkeys.

Thymic hormone production declines with age, and recent strategies for enhancing immune function in elderly people include the administration of various thymic preparations. In an effort to develop an animal model for such therapeutic intervention, the current study was undertaken. Fourteen female rhesus monkeys (Macaca mulatta), aged 18-25 years, received a 7-day course of either Thymosin Alpha One (TA1) or placebo, and in vitro and in vivo immunologic analyses were performed. The relative percentage of T-cells and T-cell subsets declined during treatment in both TA1 and placebo groups. Nevertheless, mitogen-induced proliferation and NK-cell function were increased in most monkeys that received TA1, a trend that was apparent but not statistically significant. The antibody response to tetanus toxoid vaccine was not greater in the TA1 treatment group when compared to the placebo group. These findings suggest that TA1 can be safely administered to old monkeys and that such treatment, if undertaken in a larger or more sustained trial, may be associated with demonstrable biologic activity. Further studies are warranted to determine the potential for this or similar agents to reduce the consequences of age-associated immune deficiency.

Aging