# Sustained learned immunosuppression could not prevent local allergic ear swelling in a rat model of contact hypersensitivity

## TL;DR

This study explores how learned immune responses in rats affect allergic reactions, finding that while some immune effects are preserved, local swelling remains unaffected.

## Contribution

The study demonstrates that learned immunosuppression preserves some immune effects but fails to prevent local allergic swelling in a rat model.

## Key findings

- Conditioned suppression of splenic cytokine production was preserved.
- No conditioned effects were observed in draining lymph nodes or prevention of ear swelling.
- Symptoms like itch may better reflect patient disease burden than swelling.

## Abstract

Taste-immune associative learning has been shown to mimic immunopharmacological responses. Conditioned pharmacological effects may therefore be considered as controlled drug dose reduction strategy to maintain treatment efficacy. Against this background, the present study applied an established taste-immune associative learning protocol to a rat model of DNFB-induced contact hypersensitivity. After repeated pairings of a saccharin taste (conditioned stimulus, CS) with injections of the immunosuppressant cyclosporine A (CsA, unconditioned stimulus, UCS), animals were sensitized with the hapten. Retrieval started by presenting the CS together with sub-effective doses of CsA. This procedure preserved a conditioned suppression of splenic cytokine production. Compared to full dose treated animals, conditioned effects were neither observed in draining lymph nodes nor did it prevent ear swelling. These findings suggest that active sensitization might have masked a potential conditioned reduction of local allergic reactions. Additionally, symptoms such as itch may be more suited as readout parameter since it better reflects patients’ disease burden. The present study reaffirms that learned immunopharmacological effects can be preserved using a memory-updating approach. It also emphasizes the need to further explore the usability of associative learning protocols in clinical contexts in order to address disease-specific symptoms more effectively.

The online version contains supplementary material available at 10.1038/s41598-025-13850-2.