• Mohamed G Elsakkar, Olla A Sharaki, Dina M Abdallah, Dalia K Mostafa, and Fadia T Shekondali.
• Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
• Eur. J. Pharmacol. 2016 Sep 5; 786: 100-108.

AbstractAsthma is a chronic inflammatory heterogeneous disorder initiated by a dysregulated immune response which drives disease development in susceptible individuals. Though T helper 2 (TH2) biased responses are usually linked to eosinophilic asthma, other Th cell subsets induce neutrophilic airway inflammation which provokes the most severe asthmatic phenotypes. A growing evidence highlights the role of T regulatory (Treg) cells in damping abnormal Th responses and thus inhibiting allergy and asthma. Therefore, strategies to induce or augment Treg cells hold promise for treatment and prevention of allergic airway inflammation. Recently, the link between Tumor necrosis factor-α (TNF-α) and Treg has been uncovered, and TNF-α antagonists are increasingly used in many autoimmune diseases. Yet, their benefits in allergic airway inflammation is not clarified. We investigated the effect of Adalimumab, a TNF-α antagonist, on Ovalbumin (OVA)-induced allergic airway inflammation in CD1 mice and explored its impact on Treg cells. Our results showed that Adalimumab treatment attenuated the OVA-induced increase in serum IgE, TH2 and TH1 derived inflammatory cytokines (IL-4 and IFN-γ, respectively) in bronchoalveolar lavage (BAL) fluid, suppressed recruitment of inflammatory cells in BAL fluid and lung, and inhibited BAL fluid neutrophilia. It also ameliorated goblet cell metaplasia and bronchial fibrosis. Splenocytes flow cytometry revealed increased percentage of CD4(+) CD25(+) FOXP3(+) Treg cells by Adalimumab that was associated with increase in their suppressive activity as shown by elevated BAL fluid IL-10. We conclude that the beneficial effects of Adalimumab in this CD1 neutrophilic model of allergic airway inflammation are attributed to augmentation of Treg cell number and activity. Copyright © 2016 Elsevier B.V. All rights reserved.

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