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J E Cunnick

Publications and source records attributed to J E Cunnick.

28 records · Page 2Linked to original sources
PubMed1990

Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral beta-adrenergic receptors.

Our previous work has demonstrated that presentations of mild foot-shock to Lewis rats induces a suppression of splenic and peripheral blood lymphocyte responses to nonspecific T-cell mitogens. The present study demonstrated that adrenalectomy prevented the shock-induced suppression of the mitogenic response of peripheral blood T-cells but did not attenuate the suppression of splenic T-cells. Conversely, the beta-adrenergic receptor antagonists, propranolol and nadolol, attenuated the shock-induced suppression of splenic T-cells in a dose-dependent manner but did not attenuate suppression of the blood mitogen response. These data indicate that distinct mechanisms mediate the shock-induced suppression of T-cell responsiveness to mitogens in the spleen and the peripheral blood. The results indicate that the peripheral release of catecholamines is responsible for splenic immune suppression and that adrenal hormones, which do not interact with beta-adrenergic receptors, are responsible for shock-induced suppression of blood mitogenic responses.

Adrenal Cortex Hormones↗
PubMed1990

Immobilization 12 days (but not one hour) earlier enhanced 2-deoxy-D-glucose-induced immunosuppression: evidence for stressor-induced time-dependent sensitization of the immune system.

1. Prior exposure to a stressor can either increase or decrease subsequent behavioral, neurochemical, and endocrine reactivity to stress, depending on the pattern of stress exposure. 2. Massed or frequent exposures typically induce a reduction in reactivity whereas intermittent or widely spaced exposures increase subsequent reactivity. 3. In the present study, the authors examined whether a single presentation of a temporally remote stressor would increase the immunosuppressive effects of a subsequent stressor. Specifically, the authors investigated the effectiveness of 2-deoxy-D-glucose (2-DG) in suppressing the responsiveness of splenic lymphocytes in male, Sprague-Dawley rats that received either no prior treatment, or immobilization either one hour or 12 days earlier. 4. Splenic lymphocyte responsiveness to the T-cell mitogens, Concanavalin A (Con-A) and phytohemagglutinin (PHA) was suppressed following a single injection of 2-DG. 5. The group exposed to the stress of immobilization one hour prior to 2-DG demonstrated a comparable level of immune suppression. 6. In contrast, animals immobilized 12 days prior to the administration of 2-DG showed a more pronounced suppression of immune responsiveness which was significantly greater than the other groups injected with 2-DG. 7. Neither the stress-induced elevation in corticosterone, nor the suppression of blood lymphocyte reactivity to Con-A and PHA was enhanced by prior immobilization. 8. The results indicate that the immunosuppressive effects of an acute stressor can sensitize with the passage of time.

Animals↗
PubMed1990

Stressor-induced alteration of lymphocyte proliferation in mice: evidence for enhancement of mitogenic responsiveness.

The present study evaluated the immunomodulatory effect of the administration of different intensities of electric foot shock presentations to different strains of mice. The results showed an enhancement of the mitogenic responsiveness to concanavalin A (Con A), a T-lymphocyte mitogen, that was directly related to the intensity of the electric shock presentations. However, the electric shock induced no significant alteration of the mitogenic responsiveness to lipopolysaccharide (LPS), a B-lymphocyte mitogen. These findings were evident in HLA-SW/ICR, C57BL/6N, and C3H/HEJ mice. In contrast, the C3H/HEN mice did not show any alteration of mitogenic responsiveness. The number of splenic leukocytes was not altered by the electric shock presentations in the strains that showed enhanced mitogenic responsiveness, but the C3H/HEN strain showed a leukopenia directly related to the shock intensity. In a subsequent experiment, it was demonstrated that repeated sessions of electric shock resulted in a reduction in the enhancement effect. Collectively, the results demonstrate that stressful stimulation can result in an enhancement of mitogenic responsiveness, but that such an effect is dependent on the intensity and frequency of the stressor, as well as on the strain of the subject.

Animals↗
PubMed1989

Bidirectional interaction between the central nervous system and the immune system.

We believe that any questions regarding whether the CNS can alter immune system functions no longer remain. It can conclusively be stated that the immune system is susceptible to influences of the CNS. It remains to be determined whether all classes of lymphocytes, NK cells, macrophages, polymorphonuclear leukocytes, and other antigen-processing cells are all susceptible to CNS influences. We have presented evidence that peripheral blood lymphocytes may not reflect the immunological activity of lymphocytes within lymphatic tissue after being influenced by a stressor. Thus, all types of immunological cells must be evaluated in different organs. Whether the immune system of young and old animals respond in the same way must also be determined. The sex of the animal needs to be taken into consideration. What immune responses are important to measure? Do in vitro responses reflect the ability of an animal to resist infectious disease or susceptibility to autoimmune and malignant diseases? Certainly, absence of an immune response is detrimental to health. It must be determined whether moderately suppressed immune function in multiple compartments is as detrimental as total absence of an immune response in a single immunological compartment. The data that we have presented with respect to adjuvant arthritis indicate that an immune response in the peripheral of the animal can be modified by a stressor and influence an immunopathological process. This may indicate that the most important immune compartment to evaluate with respect to altering disease susceptibility is the peripheral blood and that lymphoid tissue may be interesting, but not clinically relevant. The reasons why the peripheral blood and lymphoid tissue differ in their immunological function following exposure to a stressor must be determined. We have reviewed information indicating that lymphoid tissue is innervated and that such innervation can modify immune function. In addition, hormones released by the CNS may alter immune function. Yet, much of this data are contradictory and whether immune enhancement or suppression occurs is not clearly defined with respect to any experimental manipulation involving denervation or the addition of hormones to in vitro cultures. Whether this reflects the age of the experimental animal, the type of immune response being measured, the adequacy of the experimental procedure, background rearing conditions of the animals, the amount of noise in the animal room, the diet of the animals, or the number of animals housed per cage all remain to be determined. Our purpose has not been to provide a comprehensive review of all of the data relating to the immune system/CNS interaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Pavlovian conditioning of shock-induced suppression of lymphocyte reactivity: acquisition, extinction, and preexposure effects.

Recent research has indicated that physical stressors, such as electric shock, can suppress immune function in rats. The present study investigated whether a nonaversive stimulus that had been associated with electric shock would also impair immune function. Presentation of that conditioned stimulus (CS) by itself produced a pronounced suppression of lymphocyte proliferation in response to the nonspecific mitogens, Concanavalin-A (ConA) and Phytohemagglutinin (PHA). In further evidence of a conditioning effect, the suppression was attenuated by extinction and preexposure manipulations that degraded the associative value of the CS. These results indicate that a psychological or learned stressor can suppress immune reactivity independently of the direct effect of physically aversive stimulation or of ancillary changes in dietary and health-related habits.

Animals↗
PubMed1988

Synthesis and in-vitro cytotoxic activity of phenyl-amino-4-(p-toluenesulfinyl)-trans-1,5-hexadiene.

A novel anticancer drug, 1-phenyl-3-phenylamino-4-(p-toluenesulfinyl-trans-1,5-hexadiene has been synthesized and found to have in-vitro cytotoxicity against P388 (LD50 = 15 micrograms/ml) and L1210 (LD50 = 19 micrograms/ml) murine leukemia cells in culture. The LD50 compared favorably with that for doxorubicin. The compound was more cytotoxic to P388 tumor cells than to normal mouse splenocytes. The compound inhibited the uptake of both tritiated thymidine (42% inhibition) and tritiated uridine (24% inhibition) after 3 h of incubation when used at 5 micrograms/ml. No effect on uptake of tritiated leucine was observed during this time period. The compound was cytotoxic to normal mouse splenocytes which had been stimulated to divide by the mitogen concanavalin A. No effect was found on normal, non-dividing splenocytes. These results suggest that this novel compound is cytotoxic to leukemic cells or other rapidly dividing cells through inhibition of DNA and/or RNA synthesis.

Aniline Compounds↗
PubMed1988

Shock-induced modulation of lymphocyte responsiveness and natural killer activity: differential mechanisms of induction.

The present study was designed to determine the influence of signaled shock on splenic natural killer (NK) activity and nonspecific T-lymphocyte mitogenic responsiveness. Furthermore, experiments were conducted to examine possible mechanisms mediating this suppression. The results demonstrate that a single session of signaled shock induces suppression of splenic NK activity and T-cell response to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). However, the suppression of mitogenic responsiveness was attenuated after five daily sessions of shock, while NK activity remained suppressed. The suppression of NK function was prevented by administration of naltrexone prior to the shock session indicating mediation by opiate receptors. However, naltrexone did not prevent the shock induced suppression of mitogenic responsiveness to Con A or PHA. Diazepam was not effective in preventing the shock-induced suppression of mitogenic responses or NK activity. Collectively, these results demonstrate that mononuclear cell populations in the spleen are differentially affected by the same stressor and that the immune alterations are mediated via different pathways.

Animals↗
PubMed1988

2-deoxy-D-glucose modulation of T-lymphocyte reactivity: differential effects on lymphoid compartments.

This study was designed to evaluate the effect of glucoprivation, as induced by 2-deoxy-D-glucose (2-DG) administration, on lymphocyte mitogen reactivity in Sprague-Dawley rats. The results showed that a single injection of 2-DG decreased reactivity in both whole-blood and spleen lymphocytes, as determined by mitogenic stimulation to concanavalin A (Con A) and phytohemagglutinin (PHA). However, the suppressed reactivity for the spleen lymphocytes attenuated with repeated injections, but the whole-blood lymphocytes did not show attenuation. Mitogen assessments of lymphocytes obtained from the thymus indicated that a single injection did not induce suppressed reactivity, but repeated injections induced a pronounced suppression of responsiveness. Furthermore, mitogen assessments of mesentery lymph nodes did not show any effect of 2-DG injections. These results corroborate other findings using electric shock as the stressor, namely that different compartments of the immune system are differentially affected by a stressor.

Animals↗
PubMed1988

The central nervous system--immune system relationship.

Research investigating the pathogenesis of schizophrenia has demonstrated that cellular immune reactions, such as those that occur in known autoimmune diseases, may participate in producing alterations of the central nervous system. Furthermore, epidemiologic studies of immune-mediated diseases have suggested that activation of the central nervous system by stressful stimuli may be capable of influencing the function of the immune system. In support of that interaction, research using animal models of stress has provided valuable information as to the effect of stress on basic immune function and susceptibility to infectious disease. Possible hormonal and direct mechanisms of the central nervous system-immune system interaction have been proposed.

Autoimmune Diseases↗