Affiliations: [a] Hematology Center, University of Campinas – UNICAMP, Cidade Universitária, Campinas-SP, Brazil
| [b] Department of Medicine, Division of Hematology, Oncology and Transplantation, Vascular Biology Center, University of Minnesota, Minneapolis, MN, USA
Correspondence:
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Corresponding author: Nicola Conran, Hemocentro, Rua Carlos Chagas 480, Cidade Universitaria, Barao Geraldo. Campinas 13083-878 SP, Brazil. Tel.: +55 19 3521 8533; E-mail: conran@unicamp.br and John D. Belcher, Department of Medicine, Vascular Biology Center, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA. Tel.: +1 612 624 2611; E-mail: belcher@umn.edu.
Abstract: The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.
