REGULATORY T cells (Tregs) play a crucial role in maintaining immune tolerance to allergens, making them a promising target for allergy treatments. Low-dose interleukin-2 (IL-2LD) has been identified as a potential activator of Tregs, leading to interest in its use for managing allergic responses. The RHINIL-2 trial, a phase-2a, randomised, double-blind, placebo-controlled study, was designed to evaluate the efficacy of IL-2LD in controlling clinical responses to allergen exposure in patients with allergic rhinitis triggered by birch pollen (BP). Of the participants, 66% had coexisting asthma, and all demonstrated a total nasal symptom score (TNSS) of ≥5 after nasal exposure to BP in an environmental exposure chamber (EEC).
In the trial, patients received either IL-2 (1 MUI/day) or a placebo for 5 days, followed by weekly doses for 4 weeks. Researchers assessed the clinical response to BP exposure using TNSS, a rhinitis visual analogue scale (VAS), and spirometry. The primary endpoint was the TNSS area under the curve (TNSSΔAUC) from baseline to day 40.
Results showed that IL-2LD treatment significantly expanded Treg populations. While the TNSSΔAUC did not differ significantly between the IL-2 and placebo groups, TNSS and VAS scores were significantly reduced from baseline to day 40 within the IL-2LD group (p=0.04 and p=0.01, respectively). Spirometry readings further supported these findings, with the IL-2LD group demonstrating improvements in forced expiratory volume in one second (FEV1P) and forced mid-expiratory flow (FEF25–75%) compared to placebo (both p=0.04). However, due to the study’s short duration, no changes were observed in allergen-specific IgE or IgG4 levels, as their half-lives exceed the treatment period.
Importantly, IL-2LD was well-tolerated, with no severe adverse events reported, even among participants with asthma. These findings suggest that IL-2LD can safely modulate allergic responses, highlighting its potential as a therapeutic agent. The study lays the groundwork for larger, longer trials to more accurately assess IL-2’s therapeutic potential in allergy management.
Reference
Rosenzwajg M et al. Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial. J Allergy Clin Immunol. 2024;DOI:10.1016/j.jaci.2024.10.033
