Biomedical subjects

C L Coe

Publications and source records attributed to C L Coe.

At least 37 records · Page 2Linked to original sources

PubMed1997

Quinolinic acid and lymphocyte subsets in the intrathecal compartment as biomarkers of SIV infection and simian AIDS.

Cerebrospinal fluid (CSF) samples were collected from monkeys infected with SIVmac251 (SIV) or HIV-1/SIVmac chimeric viruses (SHIV(HXBc2) and SHIV(89.6P)) to investigate quinolinic acid (QUIN) levels in the intrathecal compartment. CSF levels of QUIN were elevated in the SIV-infected monkeys, especially in animals with end-stage disease, and in those infected with pathogenic SHIV(89.6P), but not after infection with the nonpathogenic construct SHIV(HXBc2). QUIN elevations occurred in association with reduced CD4+ and increased CD8+ lymphocytes, cellular alterations that were more pronounced in CSF than in the blood. These findings support the view that the intrathecal compartment provides a unique window on viral infection, and are in keeping with the a priori prediction that QUIN increases primarily in response to more pathogenic viral strains.

Animals↗

PubMed1997

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year.

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.

Adolescent↗

PubMed1997

Stress decreases lymphocyte cytolytic activity in the young monkey even after blockade of steroid and opiate hormone receptors.

Lymphocyte cytolytic responses were assessed in 75 infant squirrel monkeys to investigate the influence of psychosocial disturbance on immunity. Four studies evaluated alterations in lytic activity during social separations from the mother lasting for 1-7 days. Lytic responses against target cells were markedly decreased during the first day of separation, and then gradually returned toward baseline levels. Although associated with a general lymphocytopenia in vivo, lower lysis was not mediated specifically by inclusion of fewer Leu11b+ cells in the in vitro assay. Multiple physiological processes probably converge to mediate the decrease in lysis. Treatment of the infant with RU486 to block corticosteroid hormone receptors or with naltrexone to antagonize opiate hormone action did not prevent the decrease in lytic responses from occurring. This research demonstrates that psychological disturbance can significantly impact immunity, but the recovery of normal functioning by 1 week also reveals the resiliency of the immune system, paralleling the time course of the infant's behavioral adaptation to this challenge.

Animals↗

PubMed1996

Fluoxetine treatment alters leukocyte trafficking in the intrathecal compartment of the young primate.

To evaluate possible long-term effects of exposure to monoaminergic drugs, blood and cerebrospinal fluid (CSF) samples were collected from adolescent monkeys that had been treated with desipramine and fluoxetine in infancy. This evaluation focused on the number and type of leukocytes in CSF as a reflection of cell trafficking in the intrathecal compartment. Monkeys administered fluoxetine 2 years prior to the sample collection evinced significantly higher numbers of leukocytes in CSF than did either control or desipramine-treated subjects. The elevated cell count was accounted for primarily by increased numbers of CD4+ and CD8+ lymphocytes. The finding of higher cell numbers in CSF was replicated in a second sample from the fluoxetine-treated monkey obtained 1.5 years later. Because the cell profile in blood was unaffected by the prior drug treatments, these observations indicate a need for further study of serotonergic influences on regulation of the intrathecal compartment in the developing individual.

Adrenergic Uptake Inhibitors↗

PubMed1996

Surgical and psychological stressors differentially affect cytolytic responses in the rhesus monkey.

Four experiments were conducted in aged rhesus monkeys to investigate how physical and psychological stressors influence the lymphocyte cytolytic responses against two target cell lines. An initial analysis of the lytic activity of various cell subsets against K562 and RAJI target cell lines suggested that both CD3+CD8+ and several CD3- subsets were responsible for lysis of the K562 cells. The RAJI cell line, in contrast, was killed primarily by CD3-subsets. To explore the implications of this differential mediation of lysis, cytolytic activity was evaluated after a physical challenge (surgery), a psychological disturbance (social separation), and in vitro incubation of lymphocytes with cortisol. The minor surgical procedure-laparoscopic examination-resulted in a significant decrease in lymphocyte cytolytic responses against both target cells 1 week postsurgery. In contrast, psychological disturbance elicited by changes in social relations caused a dual response, differentially affecting the lysis of either K562 or RAJI cells, dependent upon the type of behavioral reaction. Incubation of lymphocytes with cortisol in vitro indicated that lysis of both targets could be affected by corticosteroids, but the high concentration required (10(-6) M) suggested that the in vivo inhibition of cytotoxicity may not have been mediated by adrenocortical activation. Overall, the results highlight the value of utilizing multiple target cell systems in the analysis of cytolytic activity, especially in studies using nonhuman primates.

Animals↗

PubMed1996

Academic examinations significantly impact immune responses, but not lung function, in healthy and well-managed asthmatic adolescents.

The influence of academic examinations on immunity and lung function was investigated in 64 adolescents to determine if stress-related changes would differ between healthy and asthmatic students. Blood samples were collected on three occasions: 1 month prior, during, and 2-3 weeks after exams. Leukocyte subsets were enumerated, and in vitro assays were conducted to assess lymphocyte proliferative and cytolytic responses and neutrophil production of superoxides. Examinations elicited significant changes in several lymphocyte subsets and marked alterations in the three functional measures in all students. However, the magnitude and pattern of change did not differ between healthy and asthmatic students. Similarly, neither mild nor more severe asthmatics showed an exam-related decrement in lung function, as reflected by peak expiratory flow rate. This research validated that examinations are a salient cause of altered immune responses, but indicates that there is not a concomitant aggravation of inflammatory disease in well-managed asthmatics.

Adolescent↗

PubMed1996

Prenatal endocrine activation alters postnatal cellular immunity in infant monkeys.

Cellular immune responses were evaluated in 35 infant rhesus monkeys generated from two types of pregnancy conditions. Pregnant females were administered either saline or adrenocorticotropic hormone (ACTH) for 2 weeks between Days 120 and 133 postconception, approximately 1 month before parturition. After birth, lymphocytes obtained from infants in the ACTH condition failed to respond as readily to allogeneic cells in mixed lymphocyte cultures, proliferated less to Con A, exhibited lower suppressor function following stimulation with Con A, and showed lower cytolytic activity against target cells. For some measures, the prenatal effect was observed more consistently in male infants. Differences were evident with these in vitro immune assays through 6 months of age, indicating that acute disturbance during the prenatal period can have lingering effects on postnatal immunity.

Adrenocorticotropic Hormone↗

PubMed1996

Interleukin-1 beta differentially affects interleukin-6 and soluble interleukin-6 receptor in the blood and central nervous system of the monkey.

Two studies were conducted to investigate whether behavioral and physiological responses induced by administration of interleukin-1 beta (IL-1 beta) were also associated with changes in interleukin-6 (IL-6) and soluble IL-6 receptor levels (sIL-6R). Following intravenous injection of rhIL-1 beta, blood and cerebrospinal fluid (CSF) samples were collected from juvenile rhesus monkeys. Marked increases in IL-6 levels were evident at 1 h in both blood and intrathecal compartments. IL-1 beta also induced significant elevations in the release of ACTH and cortisol into the blood stream, and following high doses, the monkeys evinced signs of sickness behavior. The second study characterized the IL-beta dose-response relationship showing that these physiological changes were most evident at doses between 0.5 microgram and 1.0 microgram IL-1/kg body weight. Soluble IL-6 receptor concentration was also increased, but only in plasma. There was no detectable sIL-6R in CSF. The large release of IL-6 into CSF suggests that some behavioral symptoms may be due to intrinsic changes in central nervous system activity concomitant with the alterations in peripheral physiology.

Adrenocorticotropic Hormone↗

PubMed1996

Psychological disturbance differentially alters CD4+ and CD8+ leukocytes in the blood and intrathecal compartments.

To evaluate cellular changes in the intrathecal compartment in response to psychological stress, cerebrospinal fluid (CSF) and peripheral blood (PB) samples were obtained from rhesus monkeys under baseline and challenge conditions. Juvenile monkeys separated from their social companions overnight had elevated cortisol, increased polymorphonuclear (PMN), and fewer CD4+ and CD8+ leukocytes in PB. In contrast, in CSF there were more CD4+ and fewer CD8+ leukocytes, raising the CD4/CD8 ratio. Dexamethasone given intramuscularly caused similar hematological changes; i.e. neutrophilia and lymphocytopenia with fewer CD4+ and CD8+ leukocytes in PB. However, it did not induce similar changes in CSF, indicating that the stress-related shift of CD4+ leukocytes in the intrathecal compartment involves physiological processes beyond adrenocortical steroids.

Animals↗

PubMed1996

Psychological disturbance alters thymic and adrenal hormone secretion in a parallel but independent manner.

Thymosin-alpha 1 (thymosin alpha 1) and cortisol levels were evaluated in juvenile squirrel monkeys to investigate the influence of psychological disturbance on thymic and adrenal hormone activity. Hormone levels were assessed in peripheral circulation following removal of monkeys from their social group to establish the time course of thymosin and cortisol alterations. Thymosin alpha 1 was significantly decreased after social separation in association with increased adrenocortical activity, especially during the first day after being housed alone. The temporal pattern suggested that both hormone systems are involved in the acute inhibition of functional immunity observed following this type of psychological disturbance. A second study verified that the decrement in thymosin alpha 1 levels was replicable and also sensitive to psychosocial factors that influence the level of induced disturbance. In addition, changes in thymosin secretion could be attenuated partially by pharmacological inhibition of the cortisol response and opiate hormone action. Nevertheless, the decrease in thymosin alpha 1 secretion did not appear to be a secondary consequence of adrenocortical secretion, and instead probably emanates from a general shift in neuroendocrine activity.

Animals↗

PubMed1996

Context-dependent behavioral effects of interleukin-1 in the rhesus monkey (Macaca mulatta).

The behavioral effects of recombinant human interleukin-1 alpha (IL-1) in rhesus monkeys (Macaca mulatta) were assessed in 3 experimental paradigms: (1) a testing situation in which an initial quiescent period was followed by a challenge designed to evoke agitation; (2) a novel environment with a social partner; and (3) a working memory-dependent nonspatial cognitive task. In the first two experiments we replicated our previous observations that a high IL-1 dose (25 micrograms) induces somnolence in a quiet setting within 1 h. A lower IL-1 dose (1 ng) did not have these sedative properties, but both IL-1 doses significantly reduced the number of vocalizations made by the monkeys. In contrast, when the monkeys were challenged through direct eye contact with a human experimenter, the 25 micrograms IL-1 dose significantly increased agonistic behavior. Finally, performance on a working memory-dependent task (delayed non-matching-to-sample) was unaffected by doses of IL-1 ranging from 1 to 25 micrograms, possibly because the monkeys were tested after learning the task rather than during the acquisition phase. These results demonstrate that high levels of IL-1 in peripheral circulation can have potent behavioral effects in the nonhuman primate, but that the nature of the influence will depend on the context in which the animal is evaluated. Manifestation of cytokine-induced 'sickness behavior' appears to require a permissive environment.

Agonistic Behavior↗

PubMed1996

Leukocyte trafficking in free-flowing cerebrospinal fluid of normal rhesus macaques (Macaca mulatta).

Cellular components in free-flowing cerebrospinal fluid (CSF) of normal rhesus macaques were characterized. Microscopic counting enumerated the total number of leukocytes, percentage of polymorphonuclear cells (PMN), leukocytes with nonspecific esterase (NSE), and those reducing nitro blue tetrazolium (NBT). Flow cytometric analysis further identified CD4, CD8, CD14, and CD20 positive leukocytes. These experiments established reliable techniques for evaluating cellular components in CSF from rhesus macaques and documented the difference in the CD4/CD8 ratio between peripheral blood (PB) and CSF compartments under normal physiological conditions.

Animals↗

PubMed1995

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↗

PubMed1994

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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗