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Biomedical subjects

B S Rabin

Publications and source records attributed to B S Rabin.

At least 37 records · Page 2Linked to original sources

Lymphocyte function and cytokine production during incremental exercise in active and sedentary males and females.

This study examined the effects of acute continuous incremental exercise on lymphocyte mitogenic function and cytokine production in physically active and sedentary males and females. Physically active (n = 32) and sedentary (N = 32) male and female subjects were randomly assigned to an exercise or control condition. Exercise involved a continuous incremental protocol consisting of cycling for 3 periods of 6 min at workrates corresponding to 55%, 70% and 85% VO2peak. Blood samples were drawn from a venous catheter at baseline, 6 min, 12 min and 18 min, and 2 h following completion of exercise. Relative to baseline and control condition the percentage of T (CD3+) and B cells (CD19+) significantly decreased, and the percentage of NK cells (CD3-CD16+CD56+) increased (p < 0.001) during each stage of the incremental exercise test. The proliferative response to ConA was suppressed, enhanced, or unchanged using 1.25 micrograms/ml, 2.5 micrograms/ml and 5.0 micrograms/ml ConA, respectively. The in-vitro production of IL-1 and IFN-gamma increased during each workload. In contrast IL-4 production did not change during exercise. The resting and exercise induced alterations in lymphocyte function and cytokine production were independent of gender and fitness level, and returned to baseline 2 h into recovery. The in-vitro production of IFN-gamma and IL-4 suggests that physical activity may alter the balance of TH1 and TH2 lymphocytes.

Adult↗

Interleukin 6 modulates interleukin-1-and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats.

This study examined the interaction between interleukin 6 (IL-6) and IL-1 and between IL-6 and stress on the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Coadministration of IL-6 (100 ng/rat) with IL-1 (20 or 100 mg/ rat) resulted in synergistic stimulation of the HPA axis, as determined by increased plasma levels of ACTH and corticosterone (CORT) which were greater in rats that received both cytokines than in rats receiving either cytokine alone. Concomitant administration of IL-6 (100 ng/rat) with exposure to a novelty stressor also synergistically stimulated the activation of the HPA axis, as IL-6-treated rats subjected to novelty stress had greater increases in plasma levels of ACTH and CORT than vehicle-treated rats exposed to novelty stress or rats receiving IL-6 alone. However, concomitant administration of IL-6 (100 ng/rat) did not significantly affect restraint stress induced elevation of plasma levels of ACTH and CORT, although IL-6 tended to prolong restraint stress induced elevation of plasma levels of CORT. These findings indicate a modulatory role for IL-6 stimulated HPA axis activity in response to IL-1 or a novelty psychological stressor, but not for restraint stress.

Adrenal Glands↗

Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. The influence of age at onset and negative symptoms.

BACKGROUND: Decreased interleukin-2 (IL-2) production is characteristic of active autoimmune diseases and has previously been reported in patients with schizophrenia. We attempted to replicate this finding in never-medicated schizophrenic patients and examine the possible correlation between IL-2 production and clinical variables. METHODS: The production of IL-2 was measured in equal numbers (N = 33) of DSM-III-R-diagnosed schizophrenic patients and controls who were matched for age, race, and gender. Patients were also assessed for positive, negative, and depressive symptoms. RESULTS: The production of IL-2 was significantly lower in patients than in controls. There was a significant positive correlation between IL-2 production and age at onset, and significant negative correlation between IL-2 production and negative symptom scores. In multivariate analyses, the predictive power was stronger for age at onset than for negative symptoms. Positive or depressive symptoms were unrelated to IL-2 production. CONCLUSIONS: Our finding of low IL-2 production in neuroleptic-native schizophrenic patients confirms that this finding is not confounded by medications. The correlation of low IL-2 production with younger age at onset suggests that this may be a marker for a subtype of the illness or for severity.

Acute Disease↗

Beta 2-adrenergic receptor density and cardiovascular response to mental stress.

In this study we evaluated effects of an acute experimental stressor on beta 2-adrenoceptor density and examined the relationships of baseline receptor density to cardiovascular reactions induced by stress. In addition, we investigated whether any observed alterations in receptor density were associated with concomitant redistribution of circulating lymphocyte populations. Receptor density and lymphocyte subsets were determined before and immediately following performance of a frustrating laboratory task in 22 male volunteers. Blood pressure, heart rate (HR), and plasma catecholamine concentrations were also assessed at baseline and during task performance. Parallel measurements were obtained among 11 unstressed control subjects. Receptor density increased significantly between baseline and posttask measurements, but equally so in experimental and control subjects. Numbers of T suppressor/cytotoxic and natural killer cells increased selectively among subjects assigned to the experimental (stress) condition. However, there was no association between lymphocyte subset distribution and receptor density. Interindividual variability in pretask receptor density correlated significantly with heart rate and systolic blood pressure (SBP) reactivity during the initial 3 min of mental stress, but not over the entire task period. In addition, baseline receptor density correlated with SBP (but not HR) reactivity after covariance adjustment for the concomitant change in plasma catecholamine concentrations.

Adolescent↗

Suppression of lymphocyte mitogenesis in different rat strains exposed to footshock during early diurnal and nocturnal time periods.

The present study examined stressor interactions with genotype and light/dark cycle. Male Brown Norway (BN), Fischer 344 (F344), Lewis (from two different vendors: Lew/CR and Lew/H) and Sprague Dawley (SD) rats were exposed to footshock either in the early light or early dark circadian phase. Immediately after footshock, the spleen and whole blood proliferation to PHA and Con A was assessed. To provide endocrine indices of stress, serum was measured for corticosterone and interleukin-6 (IL-6). All rats showed significant increases in serum corticosterone and IL-6 following footshock either in the light or the dark. Rat strain differences were noted in the IL-6 response, while the corticosterone response was strong for all strains. The criterion for 'suppression' of lymphocyte proliferation was p < .05 (as determined by ANOVA) compared to non-shocked controls. Spleen: with the exception of BN rats, the other strains showed suppressed spleen cell proliferation to PHA and Con A both in the light and the dark. BN rats failed to show suppression of mitogenic activity to PHA when footshock was given in the light. Peripheral blood lymphocytes: suppression in Lew rats from either vendor, and in F344 and BN rats, did not vary with time of day nor with the type of mitogen tested. SD rats did not show suppression to PHA if shocked in the light. These results highlight the generality of stressor-induced mitogenic lymphocyte proliferation during the early diurnal and nocturnal periods of the day.

Animals↗

Effect of a conditioned aversive stimulus on the immune response in three strains of rats.

In the present study we investigated the effect of a brief exposure (15 s) to a conditioned aversive stimulus (CS) on the proliferative response of spleen and peripheral blood lymphocytes (PBL) in Lewis, Fischer 344 and Sprague-Dawley rats. Plasma levels of ACTH and corticosterone were also measured. For conditioning, rats were exposed to 10 presentations of a 5 s duration foot-shock (1.6 mA) preceded by a 15 s tone. Seven days later, animals were exposed to the auditory signal without electric shock. Significant differences were found in both the kinetics and the magnitude of altered mitogenic responsiveness of PBL between the different strains of rats. Enhancement of PBL responsiveness to mitogens was observed in Fischer and Sprague-Dawley rats immediately after exposure to the CS. A significant decrease in the response of PBL to mitogens was found in Lewis and Sprague-Dawley rats 10 min after exposure to the CS. The PBL response of Sprague-Dawley and Fischer rats returned to baseline at 30 min, but not in Lewis rats. Proliferative activity of spleen lymphocytes in response to the CS was suppressed from baseline in all rat strains, but the timing and degree of suppression differed. Fischer rats had the largest percentage of suppression. The earliest suppression of spleen mitogenic function after exposure to the CS was in Fischer rats, while the Lewis rats had the latest onset of suppression, with the Sprague-Dawley rats being intermediate. Plasma levels of ACTH and corticosterone peaked at 10 min in all strains of rats. The magnitude of hormonal elevation differed in the different rat strains, suggesting that corticosterone may not have a variable immunomodulatory role in each strain. These data suggest that a brief psychological stressor results in activation of the HPA axis and is associated with strain-dependent alterations of lymphocyte responsiveness to non-specific mitogens. The short-term exposure to a CS which produces different parameters of lymphocyte functional modulation, provides a useful tool to study the mechanisms of stressor-induced immune alteration.

Adrenocorticotropic Hormone↗

Obstetric complications and autoantibodies in schizophrenia.

Our hypothesis stated that patients with schizophrenia who had obstetric complications (OC) were more likely to have autoimmune abnormalities than those without OC. OC were rated using a checklist. Anti-brain autoantibodies were measured in serum using an enzyme immunoassay. Autoantibodies to non-CNS tissues were detected using serological procedures. There were no significant differences between the groups with respect to anti-brain antibodies, but patients with OC (n = 24) had a significantly higher prevalence of autoantibodies to non-CNS tissues than patients without OC (n = 25). Both groups were receiving neuroleptic drugs. OC may contribute to autoimmune abnormalities among patients with schizophrenia.

Adult↗

Central administration of prostaglandin E2 suppresses in vitro cellular immune responses.

Research suggests that the regulation of the function of the immune system by the central nervous system (CNS) involves the integrative responses of multiple neural systems that affect neuroendocrine and sympathetic nervous systems. To determine whether prostaglandin E2 (PGE2) is involved in the modulatory mechanisms of immune system function, it was administered intracerebroventricularly (ICV) to conscious male rats. One hour later, spleen and peripheral blood lymphocytes were collected for culture with nonspecific mitogens. ICV administration of PGE2 decreased blood lymphocyte proliferative responses to the T-cell mitogens phytohemagglutinin and concanavalin A and decreased spleen lymphocyte proliferative responses to phytohemagglutinin and lipopolysaccharide (a B-lymphocyte mitogen). ICV administered PGE2 also stimulated the activity of the hypothalamic-pituitary-adrenal axis, as reflected by increased plasma concentrations of adrenocorticotropic hormone and corticosterone. Thus PGE2 may act in the CNS as a hormonal modulator of immune system function.

Adrenocorticotropic Hormone↗

Effect of one or more footshocks on spleen and blood lymphocyte proliferation in rats.

The effect of 1 (1.6 mA, 5 s), 3, 8, or 16 inescapable footshocks on the response of spleen and peripheral blood lymphocytes to nonspecific mitogenic stimulation and plasma corticosterone levels was studied in adult Lewis male rats. One footshock suppressed mitogenic activity in the spleen and this effect was comparable to 3, 8, and 16 footshocks. The maximum suppression to nonspecific mitogenic stimulation in the spleen was observed at 1 and 10 min after exposure to a single footshock and suppression of the mitogenic responses in the spleen persisted for at least 60 min. In contrast, immediately after a single footshock peripheral blood lymphocyte mitogenic function was not suppressed but instead was significantly enhanced. A significant suppression of mitogenic responsiveness of blood lymphocytes occurred 30 min after exposure to a single footshock and at 60 min the blood mitogenic activity did not differ from the home cage controls. Eight footshocks produced a significant suppression of mitogenic responses in the blood and 16 footshocks produced the greatest suppression of blood mitogenic function. These data suggest that 1 brief footshock caused activation of the HPA axis and sympathetic nervous system and resulted in significant alteration of the immune system. We suggest that noncomplex models of short-term stress may provide for a better understanding of the mechanisms underlying the development of stress reactions in the CNS and the periphery.

Animals↗

Stress-induced alteration of polymorphonuclear leukocyte function in rats.

We have used a laboratory model of footshock stress in rats to determine whether stressor-induced alterations can be induced in polymorphonuclear leukocyte (PMN) function. We studied the ability of peripheral blood PMN to ingest and kill gram-positive bacteria. A single, 1-h session of footshock stress did not alter the ability of PMN to ingest or kill bacteria. However, 3 consecutive days of a 1-h session of footshock stress significantly enhanced the phagocytic activity of PMN but suppressed the ability of PMN to kill bacteria. Thus, this experimental model suggests that both the phagocytic and killing functions of PMN can be altered by repeated exposure to a stressor.

Animals↗

Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness.

Using an enzyme immunoassay (ELISA), we measured serum interleukin-6 (IL-6) concentration in 128 schizophrenic patients (24 of whom were never medicated) and in 110 normal control subjects. Mean serum IL-6 concentration was significantly higher in the schizophrenic patients as compared with the control subjects (p = 0.009). Comparisons within the patient group revealed that serum IL-6 was significantly correlated with duration of illness (r = 0.32, p = 0.0004). After covariation for duration of illness, there was no relationship between IL-6 levels and the production of autoantibodies, clinical state, or medication status. Thus, elevated serum IL-6 levels in schizophrenia develop during the course of illness and may be related to treatment or to disease progression.

Adult↗

Effects of footshock stress upon spleen and peripheral blood lymphocyte mitogenic responses in rats with lesions of the paraventricular nuclei.

To assess the role of the hypothalamic paraventricular nucleus (PVN) in mediating stressor-induced immune alterations, male Lewis rats were subjected to a 1-h session of intermittent footshock stress or home cage conditions 6 days after receiving bilateral or sham PVN lesions. Splenic and peripheral blood lymphocyte proliferative responses to the non-specific mitogens, concanavalin A (ConA) and phytohemagglutinin (PHA), were subsequently measured as were plasma corticosterone levels. In sham-operated rats, footshock markedly elevated plasma corticosterone levels and concurrently suppressed the proliferative responses of peripheral blood and splenic lymphocytes. In PVN-lesioned rats, however, the shock-induced suppression of lymphocyte proliferation in the peripheral blood and the elevation of plasma corticosterone were significantly attenuated, while lymphocyte proliferation in the spleen was suppressed below the level of the sham-treated animals. Thus, by utilizing ablation studies, we have determined that the PVN may play a direct role in the alteration of lymphocyte function during stress, and an intact PVN buffers the effect of stress on the responsiveness of spleen lymphocytes to non-specific mitogens.

Analysis of Variance↗

Differences in serum interleukin-6 (IL-6) between healthy dextral and non-dextral subjects.

Serum interleukin-6 (IL-6) was measured in picograms/ml pg/ml using an immunoassay (ELISA) in healthy individuals (n = 148), of whom 128 were classified as dextral and 20 as non-dextral, as per a laterality questionnaire. Only 3 (15%) non-dextral individuals had serum IL-6 levels above the lower limit of the assay sensitivity as compared to 59 (46%) of dextral individuals (P < 0.013). There were no significant correlations between previously determined mitogen stimulated interleukin-2 production and autoantibodies in a subset of the same individuals. While this data does not provide casual information, it adds to the evidence of the asymmetric regulation of immune functions by the cerebral hemispheres.

Adult↗

An association between anti-hippocampal antibody concentration and lymphocyte production of IL-2 in patients with schizophrenia.

Serum concentrations of anti-hippocampal antibodies and in vitro production of the lymphokine interleukin-2 (IL-2) in response to phytohaemagglutinin (PHA) stimulation were determined using an enzyme immunoassay in 49 schizophrenic patients and 41 healthy controls. Decrease in IL-2 production, a finding frequently associated with many autoimmune diseases, was associated with an elevation in anti-hippocampal antibody optical density (AHA-OD) in schizophrenic patients. Although some control subjects had elevated antibody levels, this elevation was not associated with decreased IL-2 production. Low IL-2 production is well known to be a state marker associated with active autoimmune disease. We suggest that production of hippocampal antibody is a trait marker of vulnerability to autoimmune diseases. Thus, our finding of low IL-2 production in patients with high concentrations of hippocampal antibody is compatible with the possibility that such patients have an ongoing autoimmune process.

Adult↗

Cellular immunity in depressed, conduct disorder, and normal adolescents: role of adverse life events.

OBJECTIVE: To determine whether adolescents with major depressive disorder have disturbances in their cellular immunity and to study whether the immunological changes detected are specific to depression or are general responses to stress. METHOD: Twenty subjects with major depressive disorder, 17 nondepressed subjects with conduct disorder, and 17 normal adolescents were recruited. Subjects were assessed with a clinical interview for DSM-III-R and a modified version of the Coddington Life Events Checklist. Blood samples were drawn for total white blood cells, lymphocytes subsets, natural killer cell activity, lymphocyte proliferation response to phytohemagglutinin, and cortisol plasma levels. RESULTS: Overall, there were no significant between-group differences in any of the cellular immune measurements. Natural killer cell activity was significantly negatively correlated with past year and lifetime adverse life events across all effector-target cell ratios. Controlling for diagnoses and socioeconomic status yielded similar results. There were no significant effects of age, sex, race, sleep, nutrition, cigarette use, menstrual cycle, or cortisol on any of the immunological variables. CONCLUSIONS: In this sample of adolescents, we found that independent of the diagnoses and socioeconomic status, increases in adverse life events were associated with low natural killer cell activity.

Adolescent↗

Stressor-induced alterations of immune function: mechanisms and issues.

This paper reviews the role of catecholamines and the hypothalamic-pituitary-adrenal system in the mediation of stress-induced immune changes in both human and animal subjects. There is evidence to support the importance of these factors in mediating stressor effects on certain immune parameters, but further research is needed to define the specific circumstances in which they are relevant. Therefore, discussion of such issues as sex, genotype, stress history, environment, and stressor characteristics is provided to suggest possible ways to increase our understanding of stressor effects on immune function. Since the imposition of a stressor disrupts physiological homeostasis, understanding the capacity of the immune system to function under such conditions is of prime importance in predicting disease onset and outcome.

Animals↗

Locus coeruleus stimulation by corticotropin-releasing hormone suppresses in vitro cellular immune responses.

Previous studies have demonstrated that stressors alter cellular immune system function, and increase the activity of locus coeruleus neurons. Furthermore, stressors increase the release of corticotropin-releasing hormone (CRH) and locus coeruleus neurons are activated by CRH. Thus, the present study examined whether activation of the locus coeruleus by infusion of CRH modulates the function of blood and spleen lymphocytes assessed in vitro. CRH (100 ng) was administered into the region of the locus coeruleus in awake rats 1 hr before spleen and peripheral blood lymphocytes were collected for culture with nonspecific mitogens. Unilateral or bilateral microinfusion of CRH into the locus coeruleus produced a decrease in blood and spleen T-lymphocyte mitogenic responses to phytohemagglutinin, ConA, and an antibody to the T-lymphocyte antigen receptor. In contrast, infusion of saline into the locus coeruleus or CRH into the surrounding region of the dorsal pons did not alter spleen or blood lymphocyte responses. Plasma concentrations of adrenocorticotropic hormone, corticosterone, and IL-6 were increased by CRH infusion into the locus coeruleus. These results suggest that CRH-evoked activation of the locus coeruleus stimulates the hypophysial adrenal axis, possibly activates the sympathetic nervous system, and results in immunosuppression. Comparable changes in lymphocyte and hormone responses are produced by an aversive stimulus or a conditioned stressor, suggesting that activation of the locus coeruleus may be a component of stressor-induced immune alterations.

Adrenocorticotropic Hormone↗