Taste-immune associative learning in a rat model of allergic contact dermatitis

Allergic contact dermatitis is an inflammatory immune disease which is the cause of one of the most prevalent occupational diseases. However, since there is no specific treatment, continuous use of systemic immunosuppressive medication, such as cyclosporine A (CsA), is required. Such therapies are frequently accompanied by severe side effects, urging the need for developing alternative or supportive treatment strategies. In various immune related diseases in animals and humans, behavioral conditioning has impressively shown to reduce drug dosages - as well as treatment costs and side effects - while maintaining treatment efficacy. Here, an unconditioned stimulus (UCS, CsA) is paired several times with an unfamiliar conditioned stimulus (CS, sweet taste). Re-exposure to the CS leads to a conditioned taste avoidance/aversion (CTA) as well as learned immunosuppression, reflected by e.g. reduced cytokine levels and T cell proliferation. The present thesis aimed at analyzing the potential of this taste-immune associative learning paradigm to interfere with disease progression in a contact hypersensitivity animal model.

Using 80 mg/kg CsA as preventive treatment, this paradigm induced a strong CTA in conditioned animals, and a significant reduction of splenic interleukin (IL)-2. Moreover, a tendency of higher mast cell infiltration into the site of the allergic reaction was observed. The conditioned effect of peripheral immune parameters was evident when allergen challenge was performed on the second but not on the third retrieval trial.

In a subsequent experiment, the gustatory stimulus was presented together with 25 % of the initial drug dose (20 mg/kg CsA) as a reminder cue. This protocol prevented extinction and strengthened conditioned immunosuppression, reflected by a reinforced decrease of IL-2 cytokine level in splenocytes over six retrieval trials. However, no improvement of the objective symptom score of ear swelling was observed in conditioned animals. This finding is most probably attributed to the very strong allergic reaction induced by active DNFB sensitization and challenge, which presumably overshadowed a possible learned symptom improvement. Moreover, future experiments, comprising scratching behavior as subjective symptom score should be considered, since - in a translational aspect - relief of itch would be a great advantage for patients, contributing to a more precise characterization of the applicability of behavioral conditioning as supportive treatment in ACD.

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