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Biomedical subjects

R Ader

Publications and source records attributed to R Ader.

At least 19 recordsLinked to original sources
PubMed1992

Conditioned immunopharmacologic effects on cell-mediated immunity.

One of the several lines of evidence documenting a relationship between the brain and the immune system is the research on behaviorally induced alterations in immune reactivity. The present review concentrates on the use of immunopharmacologic agents, stress, and antigenic stimuli as unconditioned stimuli (UCSs) in the classically conditioned suppression and enhancement of cell-mediated immune reactions including host-vs-graft and graft-vs-host reactions and delayed type hypersensitivity.

Adjuvants, Immunologic↗
PubMed1992

Classic conditioning and placebo effects in crossover studies.

OBJECTIVE: To find evidence of classically conditioned placebo effects in a placebo-controlled crossover drug study. Specifically, we tested a prediction of the conditioning model that the placebo response will be greater after drug exposure than before. METHODS: Twenty-four patients with mild to moderate essential hypertension and no contraindications to atenolol participated in the study. The study design required randomized assignment to one of three groups: placebo followed by 50 mg atenolol daily, followed by no treatment, each for 1 week; atenolol followed by placebo; and atenolol followed by nothing (to show residual drug effects). Twice-daily blood pressure measurements were made by patients at home; once-weekly measurements of blood pressure and heart rate were made by a research nurse. RESULTS: Before drug treatment, there were no differences in the antihypertensive responses of patients taking placebo and patients taking nothing (difference, 0.98 mm Hg; 95% confidence interval, -0.98 to 2.93). After atenolol treatment, placebo treatment produced a significantly greater antihypertensive response than no treatment (difference, -6.09 mm Hg; 95% confidence interval, -11.81 to -0.38). Thus the placebo response after atenolol administration was more than a residual drug effect. Similar patterns were observed for heart rate but not for blood pressure readings taken in the office. CONCLUSIONS: These observations are consistent with a conditioning model of placebo effects. These findings warrant further investigation in larger studies and in other disease models.

Adult↗
PubMed1992

Conditioning as an adjunct in the pharmacotherapy of lupus erythematosus.

Several studies have provided evidence suggesting that "placebo effects" represent conditioning phenomena and that learning processes influence the response to placebo medication. This case report describes an adolescent with severe lupus erythematosus who received cyclophosphamide (CY) paired with taste (cod liver oil) and smell (rose perfume) as conditioned stimuli. The regimen was based on conditioning experiments with animals who had lupuslike autoimmune disease. After the initial pairings, the taste alone was offered between CY treatments. Over 12 months, the patient received six rather than 12 CY treatments, half the cumulative dose that might have been administered. The patient improved clinically, and 5 years later continues to do well.

Adolescent↗
PubMed1991

Conditioning of the immune response.

Experimental studies in humans and experimental animals document the acquisition and extinction of classically conditioned alterations of different parameters of humoral- and cell-mediated immune responses. Although the aversive effects of cyclophosphamide in a taste aversion learning paradigm has been the most frequently used model, conditioned immunomodulatory effects are not confined to this conditioning procedure, and they are not limited to cyclophosphamide or, for that matter, the use of immunomodulating drugs as unconditioned stimuli. Conditioned changes in immunologic reactivity have also been found to modulate the progression of spontaneously-developing or experimentally-induced pathophysiological processes in experimental animals. The available data on the immunoregulatory effects of conditioning indicate that the immune system, like other systems operating in the interests of homeostasis, is integrated with other physiological processes and is therefore influenced by and capable of influencing the brain.

Animals↗
PubMed1990

Increased pulmonary metastases and natural killer cell activity in mice following handling.

We have demonstrated that holding BALB/c female mice for two minutes per day for two weeks prior to injection of line 1, a BALB/c derived alveolar carcinoma, results in a significant increase in pulmonary metastases compared to unhandled controls. Handling did not affect splenic in vitro or in vivo natural killer (NK) cell activity but, surprisingly, was associated with increased NK cell activity in the lungs of these handled mice. These results demonstrate that a simple psychosocial manipulation may effect the metastatic process. The implications of these findings and potential mechanisms are discussed.

Animals↗
PubMed1990

The effects of handling on antibody production, mitogen responses, spleen cell number, and lymphocyte subpopulations.

The effects of a simple psychosocial manipulation, handling, on immune function in BALB/c.ByJ mice were studied. Handling for two minutes/day prior to immunization was shown to be associated with a decreased primary IgG antibody response to the protein antigen keyhole limpet hemocyanin. Handling was also associated with decreased T cell proliferative responses to Concanavalin A. No reliable changes in spleen cell number or lymphocyte subsets were found. These findings demonstrate that simply picking up an animal results in modulation of the immune response. These data are also of interest for their obvious methodological implications.

Analysis of Variance↗
PubMed1990

Altered T-lymphocyte response following aggressive encounters in mice.

Intermale aggression is a natural form of psychosocial stress that can alter a variety of physiological functions, including immune function. In Experiment 1, daily fighting between pairs of previously isolated male mice differentially altered immunological measures of T-cell responsiveness in dominant and submissive animals. Submissive mice had lower T-cell proliferation and IL-2 production, when compared to dominant, nonfought, or witness mice. Since the fighting behavior often results in wounding of the submissive animal, Experiment 2 used a relatively nonaggressive test to determine whether the immunological differences between dominant and submissive mice were due to wounding or due to the psychosocial state of dominance. Dominant mice had elevated T-cell proliferation and IL-2 production when compared to the other treatment groups. Therefore, it appears that in dominant/submissive pairs of mice a severe physical stress, such as intense fighting, influences the immune system in a different manner than psychological or mild aggressive encounters.

Aggression↗
PubMed1990

Voluntary consumption of cyclophosphamide by nondeprived Mrl-lpr/lpr and Mrl +/+ mice.

Cyclophosphamide dissolved in several dilutions of chocolate milk was presented for 20 hr daily to nondeprived, symptomatic, autoimmune Mrl-lpr/lpr and asymptomatic Mrl +/+ mice. In the absence of cyclophosphamide, daily consumption was inversely related to the concentration of the chocolate milk solutions and increased from the first to the fourth day of exposure. There were no effects of strain or sex on the consumption of plain chocolate milk. Consumption of 0.1 or 0.2 mg cyclophosphamide per ml of different dilutions of chocolate milk increased over days 1-4 and decreased on day 8. Consumption of 0.4 mg/ml cyclophosphamide did not change over days. Generally, consumption was inversely related to the cyclophosphamide concentration. Females consumed more cyclophosphamide than males. Autoimmune lpr/lpr mice consumed more cyclophosphamide than +/+ mice. Dilution of chocolate milk had no effect on consumption of cyclophosphamide. Lymphoproliferation and anti-ssDNA antibody titer were reduced by the consumption of cyclophosphamide-chocolate milk solutions. It is hypothesized that autoimmune lpr/lpr mice voluntarily consume more cyclophosphamide than asymptomatic +/+ mice in an effort to "correct" their immune system dysregulation.

Animals↗
PubMed1990

The effects of stress on the development of immunological memory following low-dose antigen priming in mice.

Observable stress effects on immune responses may be a function of the quantitative and qualitative characteristics of the stressor, and the outcome measurement of immunity. Further, the effects of stress on humoral immunity, in particular, may be sensitive to the concentrations of antigen used to elicit a response. We have studied the effects of footshock stress during the time of priming with low concentrations of antigen on the secondary response to another low dose of antigen. The secondary humoral immune response of C3H/HeJ mice to the protein antigen keyhole limpet hemocyanin was examined following footshock, exposure to the apparatus without shock, or exposure to the home cage. Footshock reproducibly depressed the IgG anti-KLH response, and the effect on the IgM response was sporadic. Initially, footshock was administered for 7 days before and 7 days after priming with low amounts of antigen. Subsequent studies demonstrated that a single footshock session delivered 24 h after priming could suppress the IgG anti-KLH response.

Animals↗
PubMed1990

Interactions between the brain and the immune system.

The observations and research described in this communication derive from a nontraditional view of the immune system. It has become abundantly clear that there are probably no organ systems or homeostatic defense mechanisms that are not, in vivo, subject to the influence of interactions between behavioral and physiological events. The complex mechanisms underlying these interactions and their relationship to health and illness, however, are imperfectly understood. The most imperfectly understood, perhaps, are the interrelationships among brain, behavior, and immune processes. Without attempting to cover all the literature, we have used stress effects and conditioning phenomena as illustrations to point out that behavior can influence immune function. We have also described data indicating that the immune system can receive and respond to neural and endocrine signals. Conversely, behavioral, neural, and endocrine responses seem to be influenced by an activated immune system. Thus, a traditional view of immune function that is confined to cellular interactions occurring within lymphoid tissues is insufficient to account for changes in immunity observed in subhuman animals and man under real world conditions. These data question seriously the notion of an autonomous immune system. Most of the research on the regulation of immune responses has been predicated on the assumption that such regulation is accomplished by the interacting components of the immune system itself, e.g. interactions among helper and suppressor T-lymphocytes, B-cells, and accessory cells that can result in the production of antibody and effector T cells. The immune system is, indeed, capable of considerable self-regulation, and immune responses can be made to take place in vitro. The functions of that component of adaptive processes known as the immune system that are of ultimate concern, however, are those that take place in vivo. There are now compelling reasons to believe that in vivo immunoregularity processes influence and are influenced by the neuroendocrine environment in which such processes actually take place--an environment that, on the one hand, can generate signals that resting and/or activated leukocytes can receive, and, on the other hand, is exquisitely sensitive to the individual's perception of and capacity to adapt to the demands of the environment. The immune system appears to be modulated, not only by feedback mechanisms mediated through neural and endocrine processes, but by feedforward mechanisms as well. The immunologic effects of learning, an essential feedforward mechanism, suggest that, like direct neural and endocrine processes, behavior can, under appropriate circumstances, serve an immunoregulatory function in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Conditioned immune responses and pharmacotherapy.

Data on the conditioned modulation of immune responses are briefly reviewed, and the successful application of conditioning operations to the pharmacotherapy of autoimmune disease in lupus-prone mice is described. These data provide the background for a discussion of the role of conditioning in pharmacotherapy and an experimental analysis of the "placebo effect" as a conditioned response.

Animals↗
PubMed1989

Repeated intraperitoneal injections of saline attenuate the antibody response to a subsequent intraperitoneal injection of antigen.

The results of two experiments with male C3H/HeJ mice indicated that repeated intraperitoneal (ip) injections of sterile saline over a 2-week period resulted in an attenuated antibody response to the subsequent ip injection of a soluble protein antigen, keyhole limpet hemocyanin. There were no differences among experimental groups that received a different number of preimmunization injections of saline, and comparable effects were obtained simply by the daily handling of mice. Neither repeated ip injections nor handling altered preimmunization (baseline) corticosterone levels, and only previously unmanipulated mice showed an elevation in corticosterone levels 30 min after ip immunization. These latter results suggest that the depressed IgM and IgG responses were not due to the immunosuppressive effects of endogenously elevated adrenocortical steroids.

Animals↗
PubMed1989

Voluntary consumption of cyclophosphamide by Mrl mice.

Fluid-deprived, lupus-prone Mrl-lpr/lpr and congenic Mrl +/+ mice were provided with a single drinking bottle containing varying concentrations of cyclophosphamide (CY) dissolved in chocolate milk. Eighteen- and 20-week-old Mrl-lpr/lpr males with manifest symptoms of autoimmune disease voluntarily consumed more of the CY solution than Mrl +/+ mice of the same age after 1 week of 1 hr/day exposures. The volume of CY-laced chocolate milk consumed was sufficient to attenuate lymphadenopathy and the elevated anti-DNA antibody titers in these animals. When testing began before the development of manifest symptoms of autoimmune disease, there were no differences between the two substrains. These results are consistent with the hypothesis that behavioral processes can act to correct homeostatic imbalances within the immune system.

Animals↗