Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial

Ann Hematol. 2019 Apr;98(4):841-849. doi: 10.1007/s00277-019-03635-9. Epub 2019 Feb 20.

Abstract

Inhaled mometasone was shown to improve pain scores and decrease soluble vascular cell adhesion molecule (sVCAM) concentration in a randomized controlled trial of nonasthmatic patients with sickle cell disease. We sought to explore potential changes in systemic inflammation as a mechanism underlying this effect. Serum samples from 41 trial participants (15 placebo- and 26 mometasone-treated) were analyzed using a 92 inflammatory marker panel at baseline and after 8 weeks of mometasone therapy. Individual marker analysis and correlation analysis were conducted. Adjusted for age, the mometasone-treated group decreased the concentration of CXCL9, CXCL11, CD40, IL-10, and IL-18 relative to placebo-treated participants. Hierarchical clustering and correlation analysis identified additional evidence for a decrease in cytokines linking to macrophage signaling and migration. There was no statistically significant change in markers of asthma and allergy, indicating that the improvement was unlikely mediated by modulation of occult reactive airway disease. This analysis of inflammatory markers suggests that decrease in macrophage activity may be involved in the mediation of the clinical benefit seen with use of inhaled mometasone in nonasthmatic patients with sickle cell disease.Trial registration: clinicaltrials.gov identifier: NCT02061202.

Keywords: Hemoglobinopathies; Inhaled corticosteroids; Macrophage activation; Sickle cell disease.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / drug therapy*
  • Asthma / blood
  • Biomarkers / blood
  • CD40 Antigens / blood
  • Chemokine CXCL11 / blood
  • Chemokine CXCL9 / blood
  • Female
  • Humans
  • Interleukin-10 / blood
  • Interleukin-18 / blood
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Mometasone Furoate / administration & dosage*
  • Pain / blood
  • Pain / drug therapy*

Substances

  • Biomarkers
  • CD40 Antigens
  • CXCL11 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL11
  • Chemokine CXCL9
  • IL10 protein, human
  • Interleukin-18
  • Mometasone Furoate
  • Interleukin-10

Associated data

  • ClinicalTrials.gov/NCT02061202