Behaviorally Conditioned Enhancement of Immune Responses

Riether²,

Doenlen³

et al. 2008

FASEB j.

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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 beta-adrenergic stimulation (terbutaline), with these effects antagonized by the beta-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."

Section: Discussionmentioning

confidence: 98%

Calcineurin inhibition in splenocytes induced by pavlovian conditioning

Riether²,

Doenlen³

et al. 2008

FASEB j.

Self Cite

“…Learned immune responses following conditioning with camphor odor and poly(I:C) have been shown to be more pronounced in young animals (3 mo old) than in older mice (24 mo old) (431). However, since effects on NK cell activity were only assessed at least 24 h after retrieval (re-exposure to the CS), the magnitude of the learned effect comparing the conditioned with the unconditioned (drug) response remains difficult to evaluate (353).…”

Section: Polyinosinic Poly-cytidylic Acidmentioning

confidence: 99%

Pavlovian Conditioning of Immunological and Neuroendocrine Functions

Hadamitzky

Lückemann

et al. 2020

Physiological Reviews

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The phenomenon of behaviorally conditioned immunological and neuroendocrine responses has been investigated for the past 100 years. The observation that peripheral immune functions can be modified by associative learning processes was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. This phenomenon was re-discovered 45 years ago as one of the most fascinating examples of the reciprocal functional interaction between behavior, the brain, and peripheral immune functions, and it established psychoneuroimmunology as a new research field. Relying on growing knowledge about efferent and afferent communication pathways between the brain, neuroendocrine system, primary and secondary immune organs, and immunocompetent cells, experimental animal studies demonstrate that cellular and humoral immune and neuroendocrine functions can be suppressed or activated via distinct associative learning protocols. These (from the classical perspective) learned immune responses are clinically relevant, since they affect the development and progression of immune-related diseases and, more importantly, are also inducible in humans. The increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provides fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient's benefit.

“…(b) Conditioned immunoactivation Although several researchers have been working on conditioned immune responses, the conditioned enhancement of antibody production is still poorly investigated (for review see [118]). However, we have been able to show enhancement of serum antibody production to a defined antigen [21].…”

Section: (A) Conditioned Immunosuppressionmentioning

confidence: 99%

Brain–immune interactions and the neural basis of disease-avoidant ingestive behaviour

Bermúdez‐Rattoni

2011

Phil. Trans. R. Soc. B

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Neuro-immune interactions are widely manifested in animal physiology. Since immunity competes for energy with other physiological functions, it is subject to a circadian trade-off between other energy-demanding processes, such as neural activity, locomotion and thermoregulation. When immunity is challenged, this trade-off is tilted to an adaptive energy protecting and reallocation strategy that is identified as 'sickness behaviour'. We review diverse disease-avoidant behaviours in the context of ingestion, indicating that several adaptive advantages have been acquired by animals (including humans) during phylogenetic evolution and by ontogenetic experiences: (i) preventing waste of energy by reducing appetite and consequently foraging/hunting (illness anorexia), (ii) avoiding unnecessary danger by promoting safe environments (preventing disease encounter by olfactory cues and illness potentiation neophobia), (iii) help fighting against pathogenic threats (hyperthermia/somnolence), and (iv) by associative learning evading specific foods or environments signalling danger (conditioned taste avoidance/aversion) and/or at the same time preparing the body to counteract by anticipatory immune responses (conditioning immunomodulation). The neurobiology behind disease-avoidant ingestive behaviours is reviewed with special emphasis on the body energy balance (intake versus expenditure) and an evolutionary psychology perspective.