Nicotine, as a novel tolerogenic adjuvant, enhances the efficacy of immunotherapy in a mouse model of allergic asthma

Ebrahim Mazloomi , Behrooz Ilkhanizadeh, Ahad Zare, Adel Mohammadzadeh, Nowruz Delirezh, Shahram Shahabi

Abstract


An increasing trend in the incidence of allergic diseases including asthma and related morbidity  and mortality is observed worldwide during the last decades. Allergen-specific immunotherapy is suggested for the treatment of some allergic diseases; nevertheless, there is always a menace of uncommon, but  life-treating reactions due to increasing the administration of allergen extract doses. Hence, improving its efficacy may reduce the required doses as well as the risk of such reactions. The current study aimed at examining the effects of nicotine (NIC), as a tolerogenic adjuvant, on the improvement of immunotherapy efficacy in a mouse model of allergic asthma. BALB/c mice were sensitized using alum and ovalbumin (OVA) on the days 0 and 7. Mice received OVA either alone or together with NIC (1 or 10 mg/kg) on the days 21, 23, and 25. Then, the mice were challenged with OVA 5% using a nebulizer  on the days 35, 38, and 41 and sacrificed the next day. Co-administration of OVA and NIC decreased the inflammation of the lung tissue, eosinophils count in the bronchoalveolar lavage (BAL) fluid, the serum level of OVA-specific immunoglobulin E, as well as interleukin (IL)-4 production, while increasing  the population of antigen-specific regulatory T-cells (Treg cells) and transforming growth factor-β/IL-4(TGF-β/IL-4) ratio compared to the OVA and control groups in a dose-dependent manner. Collectively, the findings suggest that administration of NIC plus the allergen increased immunotherapy efficacythrough decreasing allergic inflammation and allergic responses intensity, and increasingTreg cells population.


Keywords


Allergy; Asthma; Cholinergic anti-inflammatory response; Nicotine; immunotherapy.

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