Cytokine profiles in sickle cell anemia: Pathways to be unraveled

Pitanga, Thassila Nogueira; Vilas-Boas, Wendell; Cerqueira, Bruno A. V.; Seixas, Magda Oliveira; Barbosa, Cynara Gomes; Adôrno, Elisângela Vitória; Gonçalves, Marilda Souza

doi:10.4236/abb.2013.47a1002

Cited by 21 publications

(21 citation statements)

References 52 publications

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“…The activation of RBCs, leucocytes, platelets, and endothelial cells leads to the increased production of proinflammatory and anti-inflammatory cytokines, which gives SCA characteristics of a chronic inflammatory disease [69]. Our results showed increased levels of Th1 and Th17 cytokine profiles (IFN-γ, IL-12, and IL-17) and an inflammatory and regulatory cytokine pattern (IL-1β, IL-6, IL-4, and IL-10) in SCA patients at steady state.…”

Section: Discussionmentioning

confidence: 99%

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Garcia

Júnior

Soares

et al. 2020

Journal of Immunology Research

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Background. Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. Results. Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1β, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. Conclusion. In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1β, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1β and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.

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Section: Discussionmentioning

confidence: 99%

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Garcia

Júnior

Soares

et al. 2020

Journal of Immunology Research

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“…SCD is manifested by many clinical outcomes that include painful vaso-occlusive crises (VOC) triggered by sickled red blood cells, as well as leukocytes, platelets and the vascular endothelium, are elements that obstruct vessels [2,5]. The VOC causes intravascular hemolysis, RBCs rupturing and release of free hemoglobin into the plasma.…”

Section: Co-morbiditiesmentioning

confidence: 99%

Evaluation of an Undocumented Polyherbal (Faradin®) Used for the Treatment of Sickle Cell Disease in West Africa. Part I: Phytochemistry and Ex-vivo Anti-sickling Study

Adeyeye¹,

Gbadero²,

Farayola³

et al. 2017

BJPR

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Background: An undocumented complementary and alternative medicine (CAM)-Faradin® -was screened for its phytochemicals, anti-sickling effect using a clinical protocol, and toxicity. Faradin is a polyherbal made up of Zanthoxylum zanthoxyloides, Alnus glutinosa and Alchornea cordofolia. Adeyeye et al.; BJPR, 17(1): 1-14, 2017; Article no.BJPR.33605 2 Methods: The polyherbal and the individual components (coded V, M, and F) were separately screened for phytochemicals such as alkaloids, phenols, flavonoids, sterols and coumarins, using standard tests. Institutional Review Board approved clinicalprotocolinvolving4 female de-identified sickle cell patients was used for the ex-vivo anti-sickling evaluation. The negative control was phosphate-buffered saline (PBS)-washed erythrocytes treated with 2% sodium metabisulfite (SMB) to cause a hypoxic state and result in HBSS polymerization or sickling. As positive control, 2% w/v p-hydroxy benzoic acid (PHBA) solution was used. The anti-sickling effect was studied by incubating the washed erythrocytes in various concentrations of Faradin -Faradin: water v/v ratios (2.5:1 -10:1) -for 4 hours followed by further incubation with SMB for 1½ hrs. The respective samples were examined under an optical microscope and the number of sickled cells counted. Cell viability to Faradin was also done using human primary hepatocytes (HPP) and Cell Titer-Glo Luminescent assay. Results: Faradin tested positive for flavonoids, phenols, coumarins, alkaloids and antioxidants. The V component tested positive for coumarins, alkaloids and antioxidants. The M component was positive for phenols, alkaloids and antioxidants while the F component tested positive for flavonoids, phenols and antioxidants. For the anti-sickling study, the negative control (SMB treated erythrocytes) showed 20-28% increase in sickling relative to the PBS-washed. The positive control caused a reversal of sickling by decreasing the percent sickled cells from 21% to 8%. There was a dose-dependent decrease in percent sickled cells; the highest dose reduced the percent sickled cells from 21% to 2%. The activity was likely due to the phenols, polyphenols, flavonoids and antioxidants in the CAM. Cell viability of Faradin® was greater than 85%. Conclusions: Thecombined phytochemicals in the polyherbal contributed to the reversal of sickling that is similar to the positive control. Faradin has a high potential for clinical effectiveness in the management of SCD. Original Research Article

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“…They exhibit strong influence on gene transcription and the eventual functional alterations 10 . There are several reports on the involvement of cytokines in the pathophysiology of SCD; many of them showing significantly elevated levels of plasma IL-1β in these patients [11][12][13][14] . It is believed that release of cytokines in response to infection, endothelial cell activation and other injurious agents may play key role in the pathophysiology of VOC in SCD 7 .…”

Section: Introductionmentioning

confidence: 99%

IL-Iβ +3954 C / T Polymorphism and Its Clinical Associations in Egyptian Sickle Cell Disease Patients

Afifi¹,

Sedky²,

Abd-ELKareem³

et al. 2019

IJHOSCR

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Background: Sickle cell disease (SCD) is a hereditary disorder characterized by hemolytic anemia with different clinical manifestations. Patients with SCD exhibit a chronic inflammatory state and reduced length and quality of life. Interleukin-1 β (IL-1β) is important in acute and chronic diseases; and its single nucleotide polymorphisms (SNP) have been considered as predictors of prognosis in several inflammatory conditions. This study aimed at exploring IL-1β (+3954C/T) SNP as a potential genetic modifier and/or predictor of SCD clinical and laboratory phenotypes. Materials and Methods: This cross-sectional study involved 50 SCD patients and 50 age, sex and ethnicitymatched healthy individuals. IL-1β (+3954C/T) SNP was identified by PCR-RFLP. Associations between IL-1β (+3954 C/T) SNP and the clinical and laboratory profiles of patients with SCD were studied. Results: It was found that the homozygous mutant genotype TT was significantly higher in cases compared to controls [13(26%) vs. 3(6%) respectively; p=0.006, OR (95%CI): 5.505(1.460-20.756)]. The homozygous mutant genotype TT was associated with a higher mean pulmonary arterial pressure when compared to the CC and CT genotype (42.62 vs. 33.49 mmHg, p<0.001). Conclusion: There is an increased prevalence of the mutant genotype of IL-1β +3954 SNP in Egyptian SCD patients. Regarding disease complications, the mutant genotype was more prevalent in cases complicated by pulmonary hypertension. These findings point to the possible role of IL-1β +3954 SNP in the pathophysiology of SCD and its manifestations.

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Cytokine profiles in sickle cell anemia: Pathways to be unraveled

Cited by 21 publications

References 52 publications

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Evaluation of an Undocumented Polyherbal (Faradin®) Used for the Treatment of Sickle Cell Disease in West Africa. Part I: Phytochemistry and Ex-vivo Anti-sickling Study

IL-Iβ +3954 C / T Polymorphism and Its Clinical Associations in Egyptian Sickle Cell Disease Patients

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