Search PubMedSearch

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

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

Effect of maternal separation on the complement system and antibody responses in infant primates.

Hemolytic complement activity and complement protein levels were evaluated before and after psychological disturbance in the squirrel monkey. Significant increases in hemolytic complement activity were observed following separation of 6-month-old infants from their mothers. Complement protein levels were generally correlated with hemolytic activity, but did not show the same pattern of change. C3 levels did not change consistently after maternal separation, while C4 decreased significantly on Day 7, and then began to return toward basal levels by Day 14. The alterations in complement activity were associated with elevated adrenal hormone secretion, but were not directly correlated with plasma cortisol levels. A second experiment showed that increased hemolytic complement activity also occurred in juvenile squirrel monkeys following 4-hour to 7-day removals from a peer group. The effect of maternal separation on antibody responses to viral challenge was evaluated in a third experiment. Separated infant squirrel monkeys mounted a smaller antibody response than did control infants that remained with their mothers. A similar decline in antibody responses was observed in separated rhesus macaque infants, but the effect was less marked in this species. Thus, the strong effect of psychological disturbance on immunity in the squirrel monkey is probably related to its prolonged endocrine responses.

Animals

Specific antibody synthesis in vitro. IV. The correlation of in vitro and in vivo antibody response to influenza vaccine in rhesus monkeys.

Fourteen female monkeys (Macaca mulatta) received a trivalent influenza vaccine and antibody response was determined by a change in plasma antibody content (ELISA) before and after vaccine. Lymphocyte cultures were also established from these monkeys and the level of antibody response did not correlate with mitogen-induced lymphocyte blastogenesis or natural killer cell function. In vitro anti-influenza antibody synthesis, however, was found to correlate well with the in vivo response. That is, monkeys who were non-responders, as determined by lack of change in plasma antibody content, were also non-responders in vitro. Accordingly, we believe that vaccine response is not necessarily a measure of immune competence but its measurement may, none the less, have clinical utility. The excellent correlation of in vivo and in vitro response provides predictive value for the in vitro test. Furthermore, because the correlation is good, the in vitro test may be useful as a tool in immunopharmacology and toxicology.

Animals

Psychological factors capable of preventing the inhibition of antibody responses in separated infant monkeys.

The capacity of infant squirrel monkeys to mount an antibody response to viral challenge was evaluated after removal from their mothers in several social and physical environments. Control and separated infants were injected with a benign virus, the bacteriophage X174, and levels of neutralizing antibody were assessed for 3 weeks. Infants separated alone in an unfamiliar environment showed a significant reduction in antibody levels as compared to control infants. Allowing infants to remain in the home environment, either alone or with peers, prevented this inhibition of antibody responses from occurring. Similarly, providing familiar peers in the novel environment facilitated the normal expression of antibody responses. These results indicate that the trauma of maternal separation is significantly reduced when infants are familiar with the separation environment or familiar social companions are available. The reduced antibody response was associated with the highest level of adrenal activation induced by the unfamiliar separation condition, but antibody titers and plasma cortisol levels could not be specifically correlated in individual infants.

Animals

Primate vocalization: a psychobiological approach.

Scientific inquiry, for the most part, can be described as parochial. Not only are there clear demarcations between broad disciplinary categories (i.e., anatomy, physiology, psychology), but subspecialties are common within disciplines. Modern technology has made possible a trend toward greater and greater specialization. In fact, there are now areas of scientific investigation that did not exist a few years ago. This increasing specialization and its concomitant reductionism is not without its pitfalls and problems. There is a tendency to move away from the basic evolutionary concept of living organisms as organized systems functioning and adapting within an ecosystem. The laboratory scientist often ignores the inherent organization of living systems in favor of an intense pursuit of his or her particular chosen bit of the biological puzzle. However, there are still disciplines that not only subscribe to the notion of living organisms as organized systems but have made a valiant attempt to bring this concept under laboratory scrutiny. Often, in order to identify these endeavors, a technique is used to combine two or three words into one. Thus, we have several flourishing disciplines described as psychoneuroimmunology, psychoneuroendocrinology, neurochemistry, physiosociology, and so on. For the investigator who attempts a more integrated approach to the broad biological and psychological universe, the demands are heavy. He or she is faced with the need to maintain credibility in several disciplines, each of which is advancing at an accelerated pace. However, we feel that the value of an integrated approach that crosses traditional disciplinary lines will be illustrated in a small way by this article and, we hope, by the series of articles presented in this symposium section of Child Development.

Animals

Rapid cortisol and corticosteroid-binding globulin responses during pregnancy and after estrogen administration in the squirrel monkey.

Plasma cortisol and corticosteroid-binding globulin (CBG) levels were assessed in pregnant squirrel monkeys and in intact and castrated males after estrogen administration. Pregnant females showed a rapid and dramatic rise in cortisol and CBG during the first 8 weeks after conception. Estrogen treatment also caused marked elevations in cortisol and CBG. Cortisol levels increased significantly by 24 h after estrogen injection and remained elevated for 6 weeks of treatment, but a relatively greater rise in CBG resulted in a higher CBG/cortisol ratio. The data support prior research indicating that estrogen can simultaneously stimulate adrenal output and the compensatory binding of circulating cortisol by increased CBG synthesis. In addition, it appears that even in the absence of exogenous treatment, the pituitary-adrenal axis of male squirrel monkeys is stimulated by estrogen derived either from the testes or by the peripheral conversion of testosterone to estrogen.

Adrenal Glands