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Biomedical subjects

F S Dhabhar

Publications and source records attributed to F S Dhabhar.

At least 19 recordsLinked to original sources
PubMed2005

Skeleton photoperiods alter delayed-type hypersensitivity responses and reproductive function of Siberian hamsters (Phodopus sungorus).

Photoperiod (day length) can modulate immune function. Whether these photoperiodic effects on immune function are mediated directly by a circadian photoperiodic time measurement system or indirectly by nonspecific (e.g. stressful) effects of light is unknown. To discriminate between these two possibilities, Siberian hamsters (Phodopus sungorus) were housed in either long or short photoperiods (LD 16 : 8 h or LD 8 : 16 h) or in 'skeleton' long or short photoperiods (LD 1 : 14 h: LD 1 : 8 h or LD 1 : 6 h: LD 1 : 16 h). In the skeleton photoperiods, both long- and short-day animals received 2 h of light per day. After 10 weeks in their respective photoperiods, hamsters were tested for an antigen specific immune response using a delayed type hypersensitivity (DTH) model. Reproductive and endocrine responses of hamsters in each of the skeleton photoperiods were equivalent to those in standard long or short days, respectively. Hamsters in skeleton short days and LD 8 : 16 increased DTH responses compared to hamsters in both long-day groups. DTH responses were equivalent in both long-day groups. These results suggest that the influences of day length on immune function potentially are due to circadian photoperiodic time measurement systems.

Animals↗
PubMed2003

Photoperiod affects the expression of sex and species differences in leukocyte number and leukocyte trafficking in congeneric hamsters.

Sex differences in immune function are well documented. These sex differences may be modulated by social and environmental factors. Individuals of polygynous species generally exhibit more pronounced sex differences in immune parameters than individuals of monogamous species, often displaying an energetic trade-off between enhanced immunity and high mating success. During winter, animals contend with environmental conditions (e.g. low temperatures and decreased food availability) that evoke energetic-stress responses; many mammals restrict reproduction in response to photoperiod as part of an annual winter coping strategy. To test the hypothesis that extant sex and species differences in immune surveillance may be modulated by photoperiod, we examined leukocyte numbers in males and females of two closely related hamster species (Phodopus). As predicted, uniparental P. sungorus exhibited a robust sex difference, with total white blood cells, total lymphocytes, T cells, and B cells higher in females than males, during long days when reproduction occurs, but not during short days when reproduction usually stops. In contrast, biparental male and female P. campbelli exhibited comparable leukocyte numbers during both long and short days. To study sex differences in stress responses, we also examined immune cell trafficking in response to an acute (2 h) restraint stressor. During stressful challenges, it appears beneficial for immune cells to exit the blood and move to primary immune defense areas such as the skin, in preparation for potential injury or infection. Acute stress moved lymphocytes and monocytes out of the blood in all animals. Blood cortisol concentrations were increased in P. sungorus females compared to males at baseline (52%) and in response to restraint stress (38%), but only in long days. P. campbelli males and females exhibited comparable blood cortisol and stress responses during both long and short days. Our results suggest that interactions among social factors and the environment play a significant role in modulating sex and seasonal alterations in leukocyte numbers and stress responses.

Animals↗
PubMed2001

Stress-induced changes in skin barrier function in healthy women.

Despite clear exacerbation of several skin disorders by stress, the effect of psychologic or exertional stress on human skin has not been well studied. We investigated the effect of three different stressors, psychologic interview stress, sleep deprivation, and exercise, on several dermatologic measures: transepidermal water loss, recovery of skin barrier function after tape stripping, and stratum corneum water content (skin conductance). We simultaneously measured the effects of stress on plasma levels of several stress-response hormones and cytokines, natural killer cell activity, and absolute numbers of peripheral blood leukocytes. Twenty-five women participated in a laboratory psychologic interview stress, 11 women participated in one night of sleep deprivation, and 10 women participated in a 3 d exercise protocol. The interview stress caused a delay in the recovery of skin barrier function, as well as increases in plasma cortisol, norepinephrine, interleukin-1beta and interleukin-10, tumor necrosis factor-alpha, and an increase in circulating natural killer cell activity and natural killer cell number. Sleep deprivation also decreased skin barrier function recovery and increased plasma interleukin-1beta, tumor necrosis factor-alpha, and natural killer cell activity. The exercise stress did not affect skin barrier function recovery, but caused an increase in natural killer cell activity and circulating numbers of both cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to the interview stress were inversely correlated with changes in barrier function recovery. These results suggest that acute psychosocial and sleep deprivation stress disrupts skin barrier function homeostasis in women, and that this disruption may be related to stress-induced changes in cytokine secretion.

Adolescent↗
PubMed2000

Stress-induced enhancement of skin immune function: A role for gamma interferon.

Contrary to the widespread belief that stress is necessarily immunosuppressive, recent studies have shown that, under certain conditions, stress can induce a significant enhancement of a skin cell-mediated immune response [delayed-type hypersensitivity (DTH) or contact hypersensitivity]. Adrenal stress hormones and a stress-induced trafficking of leukocytes from the blood to the skin have been identified as systemic mediators of this immunoenhancement. Because gamma interferon (IFNgamma) is an important cytokine mediator of DTH, the studies described here were designed to examine its role as a local mediator of the stress-induced enhancement of skin DTH. The effect of acute stress on skin DTH was examined in wild-type and IFNgamma receptor-deficient (IFNgammaR-/-) mice that had previously been sensitized with 2,4-dinitro-1-fluorobenzene. Acutely stressed wild-type mice showed a significantly larger DTH response than nonstressed mice. In contrast, IFNgammaR-/- mice failed to show a stress-induced enhancement of skin DTH. Immunoneutralization of IFNgamma in wild-type mice significantly reduced the stress-induced enhancement of skin DTH. In addition, an inflammatory response induced by direct IFNgamma administration to the skin was significantly enhanced by acute stress. Our results suggest that IFNgamma is an important local mediator of a stress-induced enhancement of skin DTH. These studies are clinically relevant because, depending on the nature of the antigen, DTH reactions mediate numerous protective (e.g., resistance to viral, bacterial, parasitic, and fungal infections) or pathological (e.g., autoimmune reactions and contact sensitivity reactions such as that to poison ivy) immune responses.

Animals↗
PubMed2000

Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking.

Delayed-type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen, mediate beneficial (resistance to viruses, bacteria, fungi) or harmful (allergic dermatitis, autoimmunity) aspects of immunity. Contrary to the widely held notion that stress is immunosuppressive, we have shown that under certain conditions, stress can enhance immune function. DTH reactions can be studied in rats or mice by challenging the pinnae of previously sensitized animals with antigen. Studies have shown that acute stress administered immediately before antigen exposure significantly enhances skin DTH. In contrast, chronic stress significantly suppresses skin DTH. Stress-induced changes in leukocyte distribution may contribute to these bidirectional effects of stress, since acute stress induces a significant mobilization of leukocytes from the blood to the skin, whereas chronic stress suppresses leukocyte mobilization. In order to identify the hormonal mediators of the observed effects of stress, we first showed that adrenalectomy (ADX) eliminates the stress-induced enhancement of DTH. Acute administration (to ADX animals) of low doses of corticosterone and/or epinephrine significantly enhances skin DTH. In contrast, acute administration of high doses of corticosterone, low doses of dexamethasone, or chronic administration of moderate doses of corticosterone, suppress skin DTH. Thus, the timing and duration of stress may significantly affect the nature (enhancing versus suppressive) of the effects of stress on skin immune function. These results suggest that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges (e.g., wounding or infection) that may be imposed by a stressor (e.g., an aggressor). Thus, during acute stress, the brain may send a warning signal to the immune system, just as it does to other fight/flight systems in the body.

Acute Disease↗
PubMed1999

Enhancing versus suppressive effects of stress hormones on skin immune function.

Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.

Adrenalectomy↗
PubMed1998

Stress-induced enhancement of cell-mediated immunity.

We have demonstrated that acute stress induces a large-magnitude, rapid, and reversible redistribution of leukocytes from the blood to other compartments within the body. These changes in leukocyte distribution are mediated by adrenal stress hormones. Because the skin is one of the target organs of a stress-induced redistribution of leukocyes, we hypothesized that such a leukocyte redistribution could be one of the factors by which acute stress may enhance cutaneous immune function. This hypothesis was tested by examining the effects of acute stress on cutaneous delayed-type hypersensitivity (DTH). DTH reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen involved, mediate beneficial (resistance to viruses, bacteria, and fungi) or harmful (allergic dermatitis, autoimmunity) aspects of immune function. DTH was induced by challenging the pinnae of previously sensitized rats with 2,4-dinitro-1-fluorobenzene (DNFB). Experiments showed that acute stress administered immediately before the introduction of an antigenic challenge significantly enhances a cutaneous DTH response. In contrast, chronic stress suppresses cutaneous DTH. These results demonstrate a bidirectional relationship between stress and immune function, such that acute stress enhances, while chronic stress suppresses, an important class of immune responses in vivo. They also suggest that stress-induced alterations in lymphocyte redeployment within the body may play an important role in mediating these bidirectional effects of stress on cell-mediated immunity.

Animals↗
PubMed1998

Neuroendocrine-related effects of long-term, 'binge' cocaine administration: diminished individual differences in stress-induced corticosterone response.

Acute cocaine administration activates behavioral and neuroendocrine processes associated with the stress response. However, much less is known about the effects of chronic, long-term cocaine administration on neuroendocrine adaptations and individual vulnerability to stress. We hypothesized that chronic 'binge' cocaine administration may serve as a chronic pharmacological stressor leading to a hyperactivity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and alterations in its feedback mechanisms. In order to test this hypothesis, the effects of long-term (3 and 6 weeks) 'binge' pattern cocaine administration (3x15 mg/kg cocaine, i.p., daily, during the early phase of the light cycle) on body weight, adrenal gland weight, basal and stress-induced activity of the corticosterone (CORT) and basal plasma testosterone (T) levels were measured. Both 3 and 6 weeks 'binge' cocaine administration decreased body weight gain, increased the weight of adrenal glands and increased basal CORT levels. Plasma T levels were suppressed by both 3 and 6 weeks of cocaine treatment. No correlation was found between elevated CORT and low T levels at any time point. Neither chronic saline nor cocaine administration altered stress-induced CORT secretion. CORT levels 60 min following the restraint stress (recovery) were significantly lower than pre-stress basal levels after 3 and 6 weeks of cocaine, but not saline, administration. Moreover, initial individual differences in stress-induced CORT response, i.e. low and high responsivity to restraint prior to any saline or cocaine injections, were maintained in control rats but became diminished in cocaine-treated rats. These results indicate that chronic binge cocaine administration leads to sustained activation of the HPA axis and alters processes underlying individual vulnerability to stress.

Analysis of Variance↗
PubMed1998

MIF expression in the rat brain: implications for neuronal function.

BACKGROUND: The mediator known historically as macrophage migration inhibitory factor (MIF) has been identified recently as being released into the circulation by the anterior pituitary gland as a consequence of stress or during a systemic inflammatory response. Macrophages and T cells also secrete MIF, both in response to proinflammatory factors or upon stimulation with glucocorticoids. Once released, MIF "overrides" or counterregulates the immunosuppressive effects of steroids on cytokine production and immune cellular activation. To further investigate the biology of MIF and its role in the neuroendocrine system, we have studied the regional and cellular expression of MIF in brain tissue obtained from normal rats and rats administered LPS intracisternally. MATERIALS AND METHODS: Rat brain sections were analyzed by immunohistochemistry utilizing an affinity-purified, anti-MIF antibody raised to recombinant MIF, and by in situ hybridization using a digoxigenin-labeled, antisense MIF cRNA probe. The kinetics of MIF mRNA expression in brain were compared with that of IL-1, IL-6, and TNF-alpha by RT-PCR of total brain RNA. The cerebrospinal fluid content of MIF and TNF-alpha proteins was analyzed by Western blotting and ELISA. RESULTS: A strong baseline expression pattern for MIF was observed in neurons of the cortex, hypothalamus, hippocampus, cerebellum, and pons. By in situ hybridization, MIF mRNA was found predominantly in cell bodies whereas MIF protein was detected mostly within the terminal fields associated with neurons. There was a marked pattern of MIF immunoreactivity within the mossy fibers of the dentate gyrus and dendrites of the hippocampal CA3 field. These structures have been shown previously to be involved in glucocorticoid-induced tissue damage within the hippocampus, suggesting an association between MIF and targets of glucocorticoid action. The intracisternal injection of LPS increased MIF mRNA and protein expression in brain and MIF immunoreactivity was due in part to infiltrating monocytes/macrophages. MIF protein also was found to be rapidly released into the cerebrospinal fluid. This response corresponded with that of LPS-induced cytokine release and MIF mRNA expression increased in a distribution that colocalized in large part with that of TNF-alpha, IL-1 beta, and IL-6. CONCLUSION: The significant levels of baseline and inducible MIF expression in the brain and its regional association with glucocorticoid action underscore the importance of this mediator as a physiological regulator of the inflammatory stress response and further define its role within the neuroendocrine system.

Animals↗
PubMed1997

Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking.

Delayed type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses which, depending on the antigen involved, mediate beneficial (resistance to viruses, bacteria, fungi, and certain tumors) or harmful (allergic dermatitis, autoimmunity) aspects of immune function. We have shown that acute stress administered immediately before antigenic challenge results in a significant enhancement of a skin DTH response in rats. A stress-induced trafficking or redeployment of leukocytes to the skin may be one of the factors mediating this immunoenhancement. Here we investigate the effects of varying the duration, intensity, and chronicity of stress on the DTH response and on changes in blood leukocyte distribution and glucocorticoid levels. Acute stress administered for 2 h prior to antigenic challenge, significantly enhanced the DTH response. Increasing the duration of stress from 2 h to 5 h produced the same magnitude enhancement in cutaneous DTH. Moreover, increasing the intensity of acute stress produced a significantly larger enhancement of the DTH response which was accompanied by increasing magnitudes of leukocyte redeployment. In contrast, chronic stress suppressed the DTH response when it was administered for 3 weeks before sensitization and either discontinued upon sensitization, or continued an additional week until challenge, or extended for one week after challenge. The stress-induced redeployment of peripheral blood lymphocytes was attenuated with increasing exposure to chronic stress and correlated with attenuated glucocorticoid responsivity. These results suggest that stress-induced alterations in lymphocyte redeployment may play an important role in mediating the bi-directional effects of acute versus chronic stress on cell-mediated immunity in vivo.

Acute Disease↗
PubMed1997

Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress.

The present study investigated the effects of 21 days of chronic restraint stress on neural and endocrine parameters in male and female rats. Consistent with previous results, repeated restraint stress induced apical dendritic atrophy (a decrease in the number of apical branch points and dendritic length) of the CA3c pyramidal neurons in male rats. In contrast, female rats did not show significant dendritic atrophy in the apical field in response to repeated restraint stress. Female rats did show a decrease in the number of branch points in the basal dendritic tree compared to male rats in response to repeated restraint stress. Baseline and stress levels of plasma corticosterone were higher in female rats compared to male rats. Females exhibited slightly longer increases in corticosterone levels throughout the 21 days of restraint stress than males, indicating that the male corticosterone response to stress exhibited greater habituation. Plasma corticosteroid-binding globulin levels of female rats were also higher than those of male rats throughout the experiment. There was no change in plasma corticosteroid-binding globulin levels in male rats during the restraint stress, while there was a decrease in plasma corticosteroid-binding globulin levels in female rats during the restraint stress. Plasma estradiol levels in female rats also decreased in response to the chronic stress. In view of the qualitatively different dendritic atrophy found in males and females in appears unlikely that sex differences in the corticosteroid-binding globulin and corticosterone response can account for these morphological differences.

Animals↗
PubMed1997

1996 Curt P. Richter Award. Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues.

During an immune challenge it has been suggested that responding cells secrete cytokines which then stimulate the release of glucocorticoids. Glucocorticoids, in turn, are believed to bind to their receptors in target immune tissues and provide feedback inhibition on evolving immune responses. The foundations for this hypothesis have been drawn primarily from studies on animal models of autoimmune and/or inflammatory processes, and the relevance of these glucocorticoid-immune interactions to viral infections has not been extensively examined. Accordingly, we infected mice with lymphocytic choriomeningitis virus (LCMV) and measured plasma corticosterone and cytosolic glucocorticoid receptor (GR) binding at multiple time points throughout the day and throughout infection (days 3, 5, 7 and 10 post infection). Despite a vigorous immune response to this virus, LCMV infection was associated with minimal and transient increases in corticosterone secretion. Interestingly, however, significant decreases in cytosolic GR were found in immune tissues. Receptor decreases were characterized by a significant decrease in GR binding during the diurnal rise in corticosterone in the spleen and thymus of infected but not uninfected animals on days 5-10 post infection. In addition, in the morning on these days, GR binding in the spleen of infected mice was decreased compared to uninfected control mice. Following an acute injection of corticosterone on day 7 post infection, LCMV-infected animals exhibited a significantly greater decrease in splenic GR binding than uninfected control mice, suggesting an increased sensitivity to corticosterone in infected animals. No changes were found in the affinity (Kd) of the GR during infection, nor was there evidence of an infection-associated decrease in plasma corticosteroid binding globulin. The appearance of significant GR changes in the spleen and thymus, in the absence of significant elevations in corticosterone or decreases in its binding protein, suggests that cytokines and/or other factors produced within the immune tissues during infection either directly influenced GR number and/or function or influenced the local availability of corticosterone. Taken together, the results indicate that interactions between the neuroendocrine and immune systems can be modified at the level of the GR in the context of an ongoing immune response such as during a viral infection.

Adrenalectomy↗
PubMed1997

Long-term corticosteroid treatment but not chronic stress affects 11beta-hydroxysteroid dehydrogenase type I activity in rat brain and peripheral tissues.

Long-term treatment (21 days) of male rats with corticosterone in the drinking water caused a significant increase in the activity of the NADP-dependent form of 11beta-hydroxysteroid dehydrogenase (11-HSD1) in the pituitary, thymus, and spleen, (marginally in the hippocampus, amygdala and lymph nodes), without having any effect in a number of other central and peripheral tissues. In contrast, repeated restraint stress, although increasing plasma corticosterone to the same level as that observed after its administration, failed to change the activity of this key regulatory enzyme, which allows aldosterone to exert its specific effects in the presence of a large excess of corticosterone. This resistance to elevation in 11-HSD activity was also observed in the thymuses of subordinate rats during social stratification in a visible burrow system. In both cases, the circulating levels of corticosterone were much higher in stressed rats than in control animals. Factors which might account for these differences in response are discussed and compared with the situation in intact cells where, unlike in tissue homogenates, the reduction of 11-dehydrocorticosterone to corticosterone (reductase activity) appears to predominate.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Adaptation to prolonged or repeated stress--comparison between rat strains showing intrinsic differences in reactivity to acute stress.

Sprague-Dawley (SD), Fischer 344 (F344) and Lewis (LEW) rats are used in a wide variety of laboratory studies. Compared to SD and LEW rats, F344 rats show significantly greater activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to acute stress, or to immunologic challenge. These differences in HPA axis responsivity have been the basis for numerous studies investigating strain differences in immunological and behavioral parameters. However, strain differences in the adaptation of the HPA axis response to prolonged stress, or to repeated stress, have not been investigated. This series of studies demonstrates that F344 rats maintain significantly higher ACTH and corticosterone levels than SD and LEW rats during a single prolonged stress session. Furthermore, F344 rats show virtually no habituation or adaptation of the corticosterone stress response during a single prolonged (4 h) stress session, or during stress sessions repeated over a period of 10 days. In contrast, SD and LEW rats show habituation both within and across stress sessions. Strain differences in HPA axis responsivity are also reflected in the significant adrenal hypertrophy observed in F344 rats (but not in SD or LEW rats) following repeated stress. These results show that strain differences in HPA axis responsivity, which are observed under conditions of acute stress, are further amplified during prolonged or repeated stress. These differences under prolonged or repeated stress conditions may consequently magnify the behavioral and immunological differences observed between strains under basal as well as challenged conditions.

Adaptation, Physiological↗
PubMed1996

Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones.

The numbers and proportions of leukocytes in the blood provide an important representation of the state of activation of the immune system, and of the pattern of distribution of immune cells in the body. We have shown previously that acute stress induces large, rapid, and reversible changes in the distribution of peripheral blood leukocyte subpopulations in the rat. The studies described here specifically investigate the role played by adrenal steroid hormones in mediating stress-induced changes in blood leukocyte distribution. Since adrenal steroids act at two distinct receptor subtypes that show a heterogeneity of expression in immune cells and tissues, the role played by each subtype in mediating changes in leukocyte distribution is also investigated. Cyanoketone, a corticosterone (CORT) synthesis inhibitor, significantly reduced the decrease in lymphocyte numbers observed during stress and significantly enhanced the increase in neutrophil numbers observed after the cessation of stress. Acute administration of aldosterone (a specific type I adrenal steroid receptor agonist) to adrenalectomized animals did not have a significant effect on blood leukocyte numbers. In contrast, acute administration of CORT (the endogenous type I and type II receptor agonist), or RU28362 (a specific type II receptor agonist), to adrenalectomized animals produced changes in leukocyte distribution that were similar to those observed in intact animals during stress. These results suggest that CORT, acting at the type II adrenal steroid receptor, is a major mediator of the stress-induced changes in blood lymphocyte and monocyte distribution.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Stress-induced enhancement of antigen-specific cell-mediated immunity.

The studies described here demonstrate that the activation of the physiologic stress response systems of the body can enhance immune function in vivo. This enhancement is observed as a large and long lasting increase in allergic contact sensitivity or delayed-type hypersensitivity, an immune reaction which involves an Ag-specific, cell-mediated immune response. In contrast, acute stress has no effect on the course of irritant contact sensitivity, an immune reaction that does not involve an Ag-specific memory response. A comparison of infiltrating leukocyte numbers in sections of inflamed skin from unstressed and stressed animals shows that stress induces a significant and persistent increase in numbers of leukocytes at the site of the delayed-type hypersensitivity reaction. These results demonstrate that a relatively mild behavioral manipulation can enhance an important class of immune responses that mediate harmful (allergic dermatitis) as well as beneficial (resistance to certain viruses, bacteria, and tumors) aspects of immune function. The implications that these studies have for clinical, diagnostic, and experimental manipulations involving cell-mediated immune function are discussed.

Acute Disease↗
PubMed1995

Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms.

Immune cell trafficking is crucial to the performance of the surveillance as well as effector functions of the immune system. Because immune cells travel between tissues through the bloodstream, the numbers and proportions of leukocytes in the circulation provide an important representation of the state of leukocyte distribution in the body. The studies described here examine significant and selective changes in numbers and percentages of peripheral blood leukocyte subpopulations in the rat. These changes were rapidly induced under conditions of mild acute stress. Stress-induced increases in plasma corticosterone were accompanied by a significant decrease in numbers and percentages of lymphocytes, and by an increase in numbers and percentages of neutrophils. flow cytometric analysis revealed that B cell, NK cell, and monocyte numbers showed a greater stress-induced decrease than did T cells. All stress-induced changes were observed during the light (inactive) as well as the dark (active) period of the animal's diurnal cycle. Importantly, the stress-induced changes in leukocyte numbers and percentages were rapidly reversed upon the cessation of stress. Furthermore, the effects of stress were largely dependent on adrenal hormones, because the magnitude of the stress-induced changes was significantly reduced in adrenalectomized animals. Moreover, administration of corticosterone to adrenalectomized animals resulted in a close replication of stress-induced changes observed in adrenal-intact animals. These results suggest that endocrine factors released during stress modulate leukocyte trafficking and result in the redistribution of leukocytes between the blood and other immune compartments. Such a redistribution may significantly affect the ability of the immune system to respond to potential or ongoing immune challenge.

Adrenal Glands↗