For nonasthmatic patients with sickle cell disease (SCD), the inhaled steroid mometasone has been shown to provide therapeutic benefits. The mechanisms behind these benefits were recently explored and results were reported in Annals of Hematology.
In a randomized trial (ClinicalTrials.gov Identifier: NCT02061202), 92 inflammatory markers were analyzed from the serum of patients without asthma who received either inhaled mometasone (26 patients) or a placebo (15 patients). Samples were taken at baseline and at 8 weeks following the initiation of treatment.
Marker levels were measured using a quantitative real time polymerase chain reaction assay that utilized oligonucleotides coupled to antibodies for each protein. Individual marker analyses and hierarchical clustering and correlation analysis were performed, with results adjusted for age.
Asthma and allergy markers showed no statistically significant difference between groups, indicating a lack of relationship between mometasone therapy and any unidentified reactive airway disease.
However, several macrophage marker concentrations were reduced in mometasone-treated patients compared with levels for placebo-treated patients. Individual marker analyses showed reductions with mometasone relative to placebo in interleukin (IL)-10 (-20.0%; P =.021), chemokine ligand (CXCL) 9 (-12.2%; P =.024), CXCL11 (-8.0%: P =.024), IL-18 (-4.3%; P =.012), and CD40 (-1.9%; P =.029) markers. Hierarchical clustering suggested that mometasone provoked changes across myeloid lineage cytokines.
In these patients with SCD, mometasone use was correlated with reductions in macrophage markers but not in asthma-related markers, indicating that the therapeutic benefits of this approach do not involve any reactive airway disease. This steroid treatment appears to operate through macrophage behavior, though the authors recommended further studies to confirm this.
Langer AL, Leader A, Kim-Schulze S, Ginzburg Y, Merad M, Glassberg J. Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial [published online February 20, 2019]. Ann Hematol. doi: 10.1007/s00277-019-03635-9