Learned Immunosuppressive Placebo Responses Attenuate Disease Progression in a Rat Model of Arthritis

Learned Immunosuppressive Placebo Arthritis
Learned Immunosuppressive Placebo Responses – Arthritis

A recent study published in Arthritis & Rheumatology showed that inflammatory symptoms in experimentally induced arthritis in rats are attenuated by using learned immunosuppressive placebo responses.

Therapy of chronic inflammatory autoimmune diseases such as rheumatoid arthritis requires long lasting if not continuous treatment with immunosuppressive drugs. However, therapy with most small-molecule immunosuppressive drugs commonly induces unwanted toxic side effects.

In search of strategies to overcome this disadvantage, it has been suggested to use learned immunopharmacological placebo responses for drug dose reduction during therapy, while simultaneously maintaining treatment efficacy. Such approaches are based on classical conditioning of physiological responses; the bidirectional communication between the central nervous system (CNS) and the immune system.

In cooperation with Rainer H. Straub and Hubert Stangl from the laboratory of Experimental Rheumatology and Neuroendocrine Immunology, University Hospital Regensburg, Laura Lückemann and Martin Hadamitzky from the Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Germany, aimed at analyzing the potential impact of learned immunosuppression in a rat model of collagen-induced arthritis (CIA).

They showed that taste-immune conditioning together with the application of only 25 % amount of the drug led to an almost identical clinical outcome compared to 100% Cyclosporine A (CsA) administration. Conditioned animals displayed less signs of inflammation, such as swollen joints and paws, as well as less bone destruction and infiltration in surrounding tissue and improved performance in the functional grip strength test.

In a further approach, the role of β-adrenoceptors in learned immunosuppression was characterized during the course of the disease. The authors found that attenuating effects on inflammatory progression in CIA induced by conditioning were blocked by continuous application of the β-adrenoceptor antagonist nadolol. These findings suggest that learned immunosuppression seemed to be mediated via β‐adrenoceptors and might be beneficial as a supportive regimen in the treatment of chronic inflammatory autoimmune diseases by diminishing disease exacerbation.

Together, this proof-of-concept study provides first evidence in a preclinical disease model for the possible effectiveness of learned immunopharmacological strategies in clinical situations as supportive therapy together with the standard pharmacological regimen in the treatment of chronic inflammatory autoimmune diseases.

A detailed overview on the distinct paradigms of learned immunological and endocrine responses in humans and animals, and its potential applicability in patient populations and experimental disease models is provided in a recently published article in Physiological Reviews by the same authors.

Source: Arthritis Rheumatol. 2019 Sep 11. doi: 10.1002/art.41101. [Epub ahead of print]

Physiol Rev. 2019 Aug 22. doi: 10.1152/physrev.00033.2018. [Epub ahead of print]