Conditioning of drug‐induced immunomodulation in human volunteers: A European Collaborative Study

Kirschbaum, Clemens; Jabaaij, Lea; Buske‐Kirschbaum, Angelika; Hennig, Juergen; Blom, Marieke T.; Dorst, Kristien; Bauch, Joy; DiPauli, R.; Schmitz, G; Ballieux, R. E.; Hellhammer, Dirk H.

doi:10.1111/j.2044-8260.1992.tb01019.x

Cited by 30 publications

(13 citation statements)

References 14 publications

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“…Thus, cognitive strategies such as information processing or individual expectation may also have played an important role in our conditioning protocol. These considerations are supported by previous observations indicating that the information given to the subjects at the beginning of a learning protocol can modulate the conditioning of natural killer cell activity in humans (38).…”

Section: Conditioned Nkca In Humanssupporting

confidence: 69%

Conditioned increase of natural killer cell activity (NKCA) in humans.

Buske‐Kirschbaum

Kirschbaum

Stierle

et al. 1992

Psychosomatic Medicine

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Cumulating evidence suggests that immune parameters can be modified by behavioral conditioning processes in animals. The present results suggest that this also holds true for a human immune parameter. Healthy subjects were exposed to a conditioning procedure in which a neutral sherbet sweet (conditioned stimulus) was repeatedly paired with a subcutaneous injection of 0.2 mg epinephrine (unconditioned stimulus). After epinephrine administration an increase of natural killer (NK) cell activity could be observed (unconditioned response). On the conditioning test day the conditioned group showed increased NK cell activity after reexposure of the sherbet sweet combined with saline injection. No increase was found in control groups that previously received the sherbet sweet in combination with saline (saline control) or with epinephrine in an unpaired manner (unpaired control). This study supports previous findings of conditioned modulation of immune responses and represents a model to investigate conditioning processes of a human immune function.

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Section: Conditioned Nkca In Humanssupporting

confidence: 69%

Conditioned increase of natural killer cell activity (NKCA) in humans.

Buske‐Kirschbaum

Kirschbaum

Stierle

et al. 1992

Psychosomatic Medicine

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“…Although some studies produced contrasting results (73,138,191,221,298), there is now general agreement that behavioral conditioning is possible in humans (252). For example, in a study by Goebel et al (144), repeated associations between cyclosporine A and a flavored drink induced conditioned immunosuppression in healthy subjects, in which the flavored drink alone produced a suppression of the immune functions, as assessed by means of interleukin-2 (IL-2) and interferon-␥ (IFN-␥) mRNA expression, in vitro release of IL-2 and IFN-␥, as well as lymphocyte proliferation (FIGURE 10, top panel).…”

Section: Many Immune Responses Can Be Placebo Conditionedmentioning

confidence: 99%

Placebo and the New Physiology of the Doctor-Patient Relationship

Benedetti

2013

Physiological Reviews

353

320

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Modern medicine has progressed in parallel with the advancement of biochemistry, anatomy, and physiology. By using the tools of modern medicine, the physician today can treat and prevent a number of diseases through pharmacology, genetics, and physical interventions. Besides this materia medica, the patient's mind, cognitions, and emotions play a central part as well in any therapeutic outcome, as investigated by disciplines such as psychoneuroendocrinoimmunology. This review describes recent findings that give scientific evidence to the old tenet that patients must be both cured and cared for. In fact, we are today in a good position to investigate complex psychological factors, like placebo effects and the doctor-patient relationship, by using a physiological and neuroscientific approach. These intricate psychological factors can be approached through biochemistry, anatomy, and physiology, thus eliminating the old dichotomy between biology and psychology. This is both a biomedical and a philosophical enterprise that is changing the way we approach and interpret medicine and human biology. In the first case, curing the disease only is not sufficient, and care of the patient is of tantamount importance. In the second case, the philosophical debate about the mind-body interaction can find some important answers in the study of placebo effects. Therefore, maybe paradoxically, the placebo effect and the doctor-patient relationship can be approached by using the same biochemical, cellular and physiological tools of the materia medica, which represents an epochal transition from general concepts such as suggestibility and power of mind to a true physiology of the doctor-patient interaction. I.WHAT I. WHAT IS A PLACEBO RESPONSE? A. Placebos Were Introduced to Validate the Efficacy of Medical TreatmentsAncient physicians have always used bizarre and odd treatments to cure their patients, with scarce, if any, knowledge of anatomy and physiology. As the anatomical and physiological details of both the animal and the human body started emerging, the need of a scientific explanation of many medical treatments became an imperative objective of physicians and the scientific community. An important historical period whereby scientific skepticism emerged about the efficacy of some medical remedies is approximately in the second half of 1700 and involved treatments like mesmerism, perkinism, and homeopathy (178).To take mesmerism as an example, this was introduced in the second half of 1700 by Franz Anton Mesmer, who claimed to have discovered a healing fluid which he called animal magnetism. To assess the very nature and the efficacy of mesmerism in treating many diseases and symptoms, Louis XVI appointed a commission that was headed by Benjamin Franklin. This commission performed what can be considered one of the first blind assessments and sham (placebo) interventions in the history of medicine. Some women were blindfolded and asked where the mesmeric energy was being applied. As reported by the members of the commission th...

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“…A direct relation between /3-adrenergic stimulation and the increase in the number of NK cells has been inferred from studies in which fl-agonists were infused. [16][17][18][19] In addition, it was shown earlier that physical exercise, which leads to increased catecholamine levels, also affects immune parameters (see McCarthy and Dale20 for a review). It should be noted, however, that physical exercise not only influences the number of NK cells but also causes a strong increase in the number of T and B lymphocytes.2' These transient changes in immune variables could be inhibited, at least partially, by prior administration of ,-antagonists.21'22 A direct comparison with the effects of mental stress is difficult, since physical exercise results not only in an increase in the concentration of catecholamines but also in changes of the levels of many other hormones.…”

Section: Effects Of P-adrenergic Blockade On Immunologic and Cardiovamentioning

confidence: 99%

Effects of beta-adrenergic blockade on immunologic and cardiovascular changes induced by mental stress.

Benschop¹,

Nieuwenhuis²,

Tromp³

et al. 1994

Circulation

164

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BACKGROUND Acute mental stress evokes responses in the cardiovascular and the immune systems. In particular, the subset of natural killer (NK) cells is found to be responsive to mental stress. The role of beta-adrenergic mechanisms in these processes in the subject of this investigation. METHODS AND RESULTS Healthy male volunteers (n = 31) were subjected to two consecutive mental tasks. Subjects were randomly assigned to a beta-blocker (propranolol 40 mg) or a placebo group. The capsules were ingested 1 hour before the tasks. The tasks evoked sympathetic responses, as indicated by an increase in heart rate and a decrease in the preejection period. These effects were abolished under beta-blockade, indicating that effective beta-blockade was achieved. In the immune system, significant increases were found for the number of NK cells and NK cell activity in the placebo group; these increases were absent in the propranolol group. In addition, an increase in all lymphocyte subsets was observed in subjects who had ingested propranolol. This increase, however, was also observed in subjects who had received propranolol but had not performed the tasks, indicating that these non-subset-specific increases in lymphocytes were a side effect of the beta-blocker. CONCLUSIONS Mental stress induces activation of the sympathetic nervous system, with concomitant increases in the number of NK cells in the circulation. These changes were inhibited by propranolol, indicating that stress-induced increases in the number and activity of NK cells in the circulation are controlled by a beta-adrenergic mechanism.

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Conditioning of drug‐induced immunomodulation in human volunteers: A European Collaborative Study

Cited by 30 publications

References 14 publications

Conditioned increase of natural killer cell activity (NKCA) in humans.

Conditioned increase of natural killer cell activity (NKCA) in humans.

Placebo and the New Physiology of the Doctor-Patient Relationship

Effects of beta-adrenergic blockade on immunologic and cardiovascular changes induced by mental stress.

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