Human Pharmacological Conditioning of the Immune and Endocrine System: Challenges and Opportunities

Tekampe, J.; Middendorp, Henriët van; Sweep, Fred C.G.J.; Roerink, Sean H.P.P.; Hermus, A.R.M.M.; Evers, Andrea W M

doi:10.1016/bs.irn.2018.01.002

Cited by 13 publications

(9 citation statements)

References 55 publications

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“…Explorations of this are necessary to find what internal biological processes can be conditioned besides the ones already found. For example, the immune and endocrine systems can be conditioned, and the type of paired environmental cue had a significant effect on the strength of the conditioning [139][140][141][142].…”

Section: Drug Conditioning: Proto-cognitive Aspects Of Physiological ...mentioning

confidence: 99%

Cellular Signaling Pathways as Plastic, Proto-cognitive Systems: Implications for Biomedicine

Mathews¹,

Chang²,

Devlin³

et al. 2022

Preprint

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Many aspects of health and disease are modeled using the abstraction of a “pathway” – a set of protein or other subcellular activities with specified functional linkages between them. This metaphor is a paradigmatic case of a deterministic, mechanistic framework that focuses biomedical intervention strategies on altering the members of this network or the up/down-regulation links between them – rewiring the molecular hardware. However, protein pathways and transcriptional networks share important properties with neural networks and related dynamical systems, which implies that they can exhibit interesting and unexpected capabilities such as trainability (memory) and information processing in a context-sensitive manner. Specifically, they may be amenable to manipulation via their history of stimuli (equivalent to experiences, in behavioral science). If true, this would enable a new class of biomedical interventions that targets aspects of the dynamic physiological “software” implemented by pathways and gene-regulatory networks. Here, we propose an expanded view of pathways from the perspective of basal cognition. We review clinical and laboratory data supporting the idea that a broader understanding of pathways (and how they process contextual information across scales) is a limiting factor for progress in many areas of physiology and neurobiology. We argue that a fuller understanding of the functionality and tractability of pathways must go beyond a focus on the mechanistic details of their structure, to encompass their physiological history and embedding within higher levels of organization in the organism, with numerous implications for data science addressing health and disease. Exploiting tools and concepts from behavioral and cognitive sciences is not just a philosophical stance on biochemical processes; at stake is a new roadmap for overcoming the limitations of today’s pharmacological strategies and for the inference of future therapeutic interventions impacting a wide range of disease states.

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Section: Drug Conditioning: Proto-cognitive Aspects Of Physiological ...mentioning

confidence: 99%

Cellular Signaling Pathways as Plastic, Proto-cognitive Systems: Implications for Biomedicine

Mathews¹,

Chang²,

Devlin³

et al. 2022

Preprint

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“…To optimally integrate conditioning principles in drug regimens, it would therefore be important to explain the potential of pharmacological conditioning by primarily focusing on the therapeutic effects of MTX (40). Moreover, previous trials that made use of pharmacological conditioning showed a clinically meaningful reduction of side effects (35,41,42). Nevertheless, it is of utmost importance to closely monitor side effects during the whole duration of treatment.…”

Section: Testing the Hypothesismentioning

confidence: 99%

Pharmacological conditioning for juvenile idiopathic arthritis: a potential solution to reduce methotrexate intolerance

et al. 2020

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Background Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often complicated by burdensome gastro-intestinal side effects. Intolerance rates for MTX in children are high (approximately 50%) and thus far no conclusive effective treatment strategies to control for side effects have been found. To address this need, this article proposes an innovative research approach based on pharmacological conditioning, to reduce MTX intolerance. Presentation of the hypothesis A collaboration between medical psychologists, pediatric rheumatologists, pharmacologists and patient groups was set up to develop an innovative research design that may be implemented to study potential improved control of side effects in JIA, by making use of the psychobiological principles of pharmacological conditioning. In pharmacological conditioning designs, learned positive associations from drug therapies (conditioning effects) are integrated in regular treatment regimens to maximize treatment outcomes. Medication regimens with immunosuppressant drugs that made use of pharmacological conditioning principles have been shown to lead to optimized therapeutic effects with reduced drug dosing, which might ultimately cause a reduction in side effects. Testing the hypothesis This research design is tailored to serve the needs of the JIA patient group. We developed a research design in collaboration with an interdisciplinary research group consisting of patient representatives, pediatric rheumatologists, pharmacologists, and medical psychologists. Implications of the hypothesis Based on previous experimental and clinical findings of pharmacological conditioning with immune responses, we propose that the JIA patient group is particularly suited to benefit from a pharmacological conditioning design. Moreover, findings from this study may potentially also be promising for other patient groups that endure long-lasting drug therapies.

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“…First, an association is formed during the acquisition phase, in which two stimuli are repeatedly presented at the same time. In the second phase, the strength of the learned association is subsequently tested during the evocation phase (see Figure 3 for an overview of a conditioning paradigm) [23,45]. In the acquisition phase, an initial neutral stimulus, like a gustatory or olfactory stimulus (conditioned stimulus, CS), is paired with an unconditioned stimulus (UCS), for example an immunomodulating drug.…”

Section: The Learned Immune Responsementioning

confidence: 99%

“…In conditioning paradigms, it has shown that after this association has been formed, re-exposure of the CS alone, without the presence of the immunomodulating drug in the evocation phase, can now demonstrate a conditioned response (CR; Figure 3). This conditioned immune response is present on a behavioral level, for example by a conditioned taste aversion, and on an immunological level by mimicking the initial drug effect [23,45]…”

Section: The Learned Immune Responsementioning

confidence: 99%

The role of placebo effects in immune-related conditions: mechanisms and clinical considerations

Smits

Veldhuijzen

Wulffraat

et al. 2018

Expert Review of Clinical Immunology

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Placebo effects are powerful modulators in clinical outcomes and can either result in treatment benefits or harms, known as placebo and nocebo effects. To harness these outcomes, it is important to focus on the underlying processes that steer these effects, namely by learning through expectations and conditioning. In this review, we focus on the influence of placebo effects on subjective and physiological levels of immune-related conditions (e.g. lymphocyte proliferation, cytokine production or other inflammatory markers). Areas covered: A literature search is conducted in the databases PubMed and PsychInfo by making use of keywords such as 'expectations', 'classical conditioning', 'cytokines', 'immune system', 'learned immunosuppression', and covers studies done in animals, experimental studies in healthy controls as well as studies performed in immune-related patient populations. Expert commentary: We report on the presence of placebo effects in RCTs in immune-related conditions and review findings that demonstrate the ability to learn immune responses in both experimental animal and human placebo studies making use of conditioning paradigms with immunomodulating drug agents. We also discuss results to utilize placebo effects by means of classical conditioning principles in medication regimens for patient populations and elaborate on promising findings of preliminary studies focusing on this topic.

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Human Pharmacological Conditioning of the Immune and Endocrine System: Challenges and Opportunities

Cited by 13 publications

References 55 publications

Cellular Signaling Pathways as Plastic, Proto-cognitive Systems: Implications for Biomedicine

Cellular Signaling Pathways as Plastic, Proto-cognitive Systems: Implications for Biomedicine

Pharmacological conditioning for juvenile idiopathic arthritis: a potential solution to reduce methotrexate intolerance

The role of placebo effects in immune-related conditions: mechanisms and clinical considerations

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