Efficacy of low-dose IL-1 as an adjuvant in allergy immunotherapy

Abstract

Prérequis/contexte

Allergen-specific immunotherapy (AIT) remains the only disease-modifying treatment for allergy, involving the gradual administration of allergens in escalating doses to desensitize the immune system. However, AIT is limited by long treatment duration, inconsistent efficacy, and the risk of adverse reactions. Various adjuvants are being developed to overcome these challenges.

Objectifs

We have previously shown that Interleukin-1 (IL-1) suppresses allergic responses. In this study, we investigated the potential of low-dose IL-1 as an adjuvant in AIT and compared its efficacy with that of monophosphoryl lipid A (MPLA), a detoxified carbohydrate-based Toll-like receptor 4 (TLR4) agonist with an immunostimulatory and safe profile.

Méthodes

Using an established mouse model of allergic anaphylaxis, female mice were sensitized to ovalbumin (OVA) and then treated with either IL-1/OVA or MPLA/OVA over short- and long-term protocols. Sensitization was assessed by measuring plasma levels of OVA-specific IgG1 and IgE, while allergic severity was assessed by mast cell protease-1 (mMCP-1) levels, body temperature drops, and clinical symptom scoring. Additionally, peritoneal mast cell receptor expression was assessed using flow cytometry.

Résultats/discussions

Our results showed that MPLA-treated mice exhibited increased allergic responses, whereas IL-1 treatment significantly improved clinical outcomes. IL-1 reduced the drop in body temperature, decreased clinical scores, and improved the IgG: IgE ratio by increasing OVA-specific IgG production. Furthermore, IL-1 upregulated the FcgRIIb: FceRI ratio on mast cells, indicating increased regulatory activity and attenuated mast cell degranulation. These findings demonstrate the ability of IL-1 to attenuate allergic responses and to deviate pathogenic IgE responses towards protective IgG responses while limiting mast cell degranulation, a key goal in AIT.

Conclusion

In conclusion, low-dose IL-1 shows potential as an effective adjuvant for AIT with improved immunomodulatory effects and safety compared to MPLA. These results pave the way for optimizing AIT strategies to develop more effective therapies for allergic diseases.