The following is a summary of “Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma,” published in the August 2024 issue of Allergy and Immunology by Howell et al.
Mepolizumab, an anti-interleukin-5 monoclonal antibody, is an established treatment for severe eosinophilic asthma (SEA) that effectively reduces exacerbations. However, patients may still experience residual airway inflammation and subsequent exacerbations despite mepolizumab therapy, necessitating the use of oral corticosteroids to manage these persistent issues.
This study aimed to investigate the responsiveness of residual airway inflammation to corticosteroid therapy following mepolizumab treatment, with the goal of identifying potentially treatable inflammatory mechanisms beyond the IL-5 pathway.
The MAPLE trial was a multi-center, randomized, double-blind, placebo-controlled crossover study involving 27 patients with SEA on stable mepolizumab treatment. Participants received high-dose oral prednisolone for 2 weeks. Paired sputum (n=16) and plasma (n=25) samples were collected and analyzed using high-throughput Olink® proteomics. Additionally, sputum proteins were assessed using ELISA.
Prednisolone treatment led to a significant downregulation of sputum proteins associated with type-2 inflammation and chemotaxis, including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and ST2 receptor. Furthermore, prednisolone reduced levels of cell adhesion molecules, prostaglandin synthases, mast cell tryptases, and MMP1, MMP12, and neuroimmune mediators. In contrast, neutrophilic pathways were found to be upregulated. In plasma, type-2 inflammatory proteins were also downregulated, alongside IL-12, IFN-γ, and IP-10 increases, while IL-10 and amphiregulin levels were elevated.
Prednisolone exhibits broad anti-inflammatory effects in patients with SEA receiving mepolizumab, targeting multiple inflammatory pathways and mediators. These findings suggest that corticosteroids may address residual inflammation in this patient population, improving the management of ongoing exacerbations despite IL-5 pathway inhibition.
Source: sciencedirect.com/science/article/pii/S0091674924007772
