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High levels of proinflammatory cytokines IL-6 and IL-8 are associated with a poor clinical outcome in sickle cell anemia

Abstract

Sickle cell anemia (SCA) pathophysiology is characterized by the activation of sickle red blood cells, reticulocytes, leukocytes, platelets, and endothelial cells, and with the expression of several inflammatory molecules. Therefore, it is conceivable that variations in levels of proinflammatory cytokines may act as a signaling of differential clinical course in SCA. Here, we evaluated the clinical impact of proinflammatory cytokines interleukin 1-β (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8) in 79 patients with SCA, followed in a single reference center from northeastern Brazil. The main clinical/laboratory data were obtained from patient interview and medical records. The proinflammatory markers IL-1β, IL-6, and IL-8 were evaluated by using commercially available enzyme-linked immunosorbent assay kits. According to levels of the proinflammatory markers, we observed that patients who had a higher frequency of VOC per year (P = 0.0236), acute chest syndrome (P = 0.01), leg ulcers (P = 0.0001), osteonecrosis (P = 0.0006), stroke (P = 0.0486), and priapism (P = 0.0347) had higher IL-6 levels compared with patients without these clinical complications. Furthermore, increased levels of IL-8 were found in patients who presented leg ulcers (P = 0.0184). No significant difference was found for IL-1β levels (P > 0.05). In summary, the present study emphasizes the role of inflammation in SCA pathophysiology, reveals an association of IL-8 levels and leg ulcer occurrence, and indicates that IL-6 levels can be used as a useful predictor for poor outcomes in SCA.

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Acknowledgments

The authors acknowledge all subjects and their parents for cooperation in this study.

Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant No. 2014/00984-3), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundo de Apoio ao Ensino, Pesquisa e Extensão-FAEPEX/UNICAMP (Brazil). DAP-M was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant No. 2017/23117-1).

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IFD performed experiments, analyzed and interpreted data, performed statistical analyses, and drafted the manuscript. DAP-M, MJVCS, RTDO, AEA, CL, and DMA performed experiments, updated the clinical data, and reviewed the manuscript. MHSLB, ASA, FFC, and MAB recruited patients, updated the clinical data, and reviewed the manuscript. ARL-A analyzed and interpreted data, performed statistical analyses, and reviewed the manuscript. MFS and MNNS conceived and designed the study and reviewed the manuscript. MNNS gave the final approval of the version to be submitted.

Corresponding author

Correspondence to Magnun N. N. Santos.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

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Informed consent was obtained from all patients for being included in the study.

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Domingos, I.F., Pereira-Martins, D.A., Sobreira, M.J.V.C. et al. High levels of proinflammatory cytokines IL-6 and IL-8 are associated with a poor clinical outcome in sickle cell anemia. Ann Hematol 99, 947–953 (2020). https://doi.org/10.1007/s00277-020-03978-8

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  • DOI: https://doi.org/10.1007/s00277-020-03978-8

Keywords

  • Proinflammatory cytokines
  • Clinical complications
  • Leg ulcers
  • Sickle cell anemia