Background:
Sickle cell anemia (SCA) is a hemolytic disease where vaso-occlusive events (VOE) serve as a primary pathophysiological mechanism. Treatment is standardly based on hydroxyurea (HU), which increases fetal hemoglobin synthesis and reduces leukocyte counts. While monocytes are known to contribute to vascular dysfunction and coagulation through tissue factor (TF) expression, the specific impact of HU on distinct monocyte subsets and their inflammatory potential remains unclear.
Abstract:
Methods: This study investigated monocyte subset frequencies and their response to HU therapy in 37 pediatric SCA patients (17 taking HU, 20 not taking HU). Monocyte phenotypes—classical ($CD14^{++}CD16^{-}$), intermediate ($CD14^{+}CD16^{+}$), and patrolling ($CD14^{dim}CD16^{+}$)—were analyzed via flow cytometry. The cells’ ability to produce TF and pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6, IL-8) upon LPS stimulation was also tested.
Results: Patients not undergoing HU therapy showed higher frequencies of classical monocytes. HU treatment was associated with a shift toward the patrolling phenotype and a significant reduction in the production of TF and cytokines (TNF-$\alpha$, IL-1$\beta$, and IL-6) by LPS-activated monocytes. Furthermore, HU therapy dramatically dampened the polyfunctional capacity of monocytes to produce multiple cytokines simultaneously. High frequencies of TF-expressing monocytes were specifically associated with a previous history of VOE.
Conclusion: Hydroxyurea alters the distribution of monocyte subsets and reduces their inflammatory and pro-coagulant potential. Classical monocytes appear to be the primary drivers of the cytokine storm and vaso-occlusion in SCA, and HU effectively dampens this activity.
Keywords: sickle cell disease; hydroxyurea; monocyte subsets; tissue factor; inflammation; vaso-occlusive events.
Clique aqui
- Data de Publicação: 15/10/2019
- Autores: Caroline C.Guarda1,2, Paulo S. M. Silveira-Mattos2,3,4,5, SètondjiC. M.A.Yahouédéhou1,2, Rayra P. Santiago1,2, Milena M.Aleluia1, CamyllaV. B. Figueiredo1,2, Luciana M. Fiuza1,2, Suellen P. Carvalho1,2, Rodrigo M. Oliveira1,2, Valma M. L. Nascimento6, Nívea F. Luz3, Valéria M. Borges 2,3, Bruno B.Andrade 2,3,4,5,7,8 & Marilda S.Gonçalves1,2
