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Calcineurin inhibition in splenocytes induced by pavlovian conditioning
Author(s) -
Pacheco-Lóipez Gustavo,
Riether Carsten,
Doenlen Raphael,
Engler Harald,
Niemi Maj-Britt,
Engler Andrea,
Kavelaars Annemieke,
Heijnen Cobi J.,
Schedlowski Manfred
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-115683
Subject(s) - calcineurin , immunosuppression , pharmacology , splenocyte , saccharin , cytokine , immune system , immunology , endocrinology , medicine , transplantation
Pavlovian conditioning is one of the major neurobiological mechanisms of placebo effects, potentially influencing the course of specific diseases and the response to a pharmacological therapy, such as immunosuppression. In our study with behaviorally conditioned rats, a relevant taste (0.2% saccharin) preceded the application of the immunosuppressive drug cyclosporin A (CsA), a specific calcineurin (CaN) inhibitor. Our results demonstrate that through pavlovian conditioning the particular pharmacological properties of CsA can be transferred to a neutral taste, i.e ., CaN activity was inhibited in splenocytes from conditioned rats after reexposure to the gustatory stimulus. Concomitant immune consequences were observed on ex vivo mitogenic challenge (anti‐CD3). Particularly, Th1‐cytokine, but not Th2‐cytokine, production and cell proliferation were impeded. Appropriate pharmacological and behavioral controls certify that all these changes in T‐lymphocyte reactivity are attributable to mere taste reexposure. Furthermore, the underlying sympathetic‐lymphocyte interaction was revealed modeling the conditioned response in vitro . CaN activity in CD4 + T lymphocytes is reduced by β‐adrenergic stimulation (terbutaline), with these effects antagonized by the β ‐adrenoreceptor antagonist nadolol. In summary, CaN was identified as the intracellular target for inducing conditioned immunosuppression by CsA, contributing to our understanding of the intracellular mechanisms behind “learned placebo effects.”—Pacheco‐López, G., Riether, C., Doenlen, R., Engler, H., Niemi, M.‐B., Engler, A., Kavelaars, A., Heijnen, C. J., Schedlowski, M. Calcineurin inhibition in splenocytes induced by pavlovian conditioning. FASEB J . 23, 1161–1167 (2009)