Are IL-1 family cytokines important in management of sickle cell disease in Sub-Saharan Africa patients?

Frontiers in Immunology · 12 authors, 3 centres

AI SUMMARY

FIDELITY 100%

POPULATION90 sickle cell disease patients (SSFA2, SFA2, SC genotypes) aged 4–55 years in Côte d'Ivoire

INTERVENTIONMeasurement of 13 plasma cytokines/chemokines (IL-1β, IL-18, IL-33, IL-6, IL-8, IL-10, TNFα, IFN-α2, IFN-γ, MCP-1, IL-12p70, IL-17A, IL-23) using BioLegend LEGENDplex Human Inflammation Panel

COMPARISONCrisis patients (n=56) vs. steady state patients (n=34); also compared by hemoglobin type and complication type

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TL;DR

This study measured IL-1 family cytokines (IL-1β, IL-18, IL-33) in 90 sickle cell disease patients in Côte d'Ivoire, comparing those in crisis versus steady state. IL-1β and IL-18 were significantly elevated during crisis, while IL-33 was significantly lower, suggesting these cytokines play a role in clinical exacerbation. The findings point toward potential new therapeutic targets and biomarkers for SCD management in Sub-Saharan Africa.

Full summary

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**Background:** Sickle cell disease (SCD) is the most common genetic disease in Africa, with the sickle cell gene present in 10–45% of the population in many countries. Inflammation is a fundamental component of SCD pathophysiology, driven by HbS polymerization, hemolysis, and release of damage-associated molecular patterns. Cytokines of the IL-1 family (IL-1β, IL-18, IL-33) are key inflammatory mediators, but few studies have investigated their role in SCD in Sub-Saharan Africa. This study aimed to estimate cytokine levels, particularly IL-1 family cytokines, in SCD patients in Côte d'Ivoire to evaluate their potential as biomarkers of severity and prognosis.

**Methods:** A prospective case-control study recruited 90 SCD patients (48 women, 42 men; mean age 20.9 ± 14.6 years in steady state, 27.3 ± 13.1 years in crisis) from the National Blood Transfusion Center in Abidjan, Côte d'Ivoire. Patients were divided into crisis (n=56) and steady state (n=34) groups. Hemoglobin types were determined by electrophoresis: 46 SSFA2 (51.1%), 28 SFA2 (31.1%), and 16 SC (17.8%). Plasma cytokines were measured using the BioLegend LEGENDplex Human Inflammation Panel, quantifying 13 cytokines/chemokines simultaneously via flow cytometry. Statistical analysis used SPSS version 22.0, with Student's t-test, ANOVA, Mann-Whitney U, or Kruskal-Wallis tests as appropriate; p ≤ 0.05 was considered significant.

**Key Results:** IL-1β was significantly elevated in crisis (43.21 ± 181.42 pg/ml) vs. steady state (3.50 ± 6.65 pg/ml; p=0.03). IL-18 was also significantly higher in crisis (1433.02 ± 1901.54 pg/ml) vs. steady state (667.82 ± 1049.31 pg/ml; p=0.01). Conversely, IL-33 was significantly lower in crisis (6.13 ± 13.60 pg/ml) vs. steady state (13.42 ± 29.18 pg/ml; p=0.04). IL-6 (p=0.01) and IL-8 (p=0.0024) were also significantly elevated in crisis, while IL-10 and TNFα did not reach statistical significance. Stroke was the most common complication (46%), followed by leg ulcer (27%) and osteonecrosis (10.8%). In stroke patients, IL-1β and IL-18 were significantly increased (p<0.001 vs. steady state), while IL-33 was decreased (p<0.05 vs. steady state). By hemoglobin type, SFA2 patients showed significantly higher IL-1β during crisis (p=0.02), SC patients showed higher IL-18 (p=0.01), and SSFA2 patients showed lower IL-33 (p=0.000096). Hemolytic anemia accounted for 55% of crises and vaso-occlusive crisis for 45%, with trends toward higher inflammatory cytokines in hemolytic anemia.

**Clinical Implications:** This study provides the first cytokine profiling of SCD patients in Côte d'Ivoire and demonstrates that IL-1 family cytokines are significantly dysregulated during SCD crisis. The substantial increase in IL-1β and IL-18 during crisis, particularly in stroke patients, suggests these cytokines may serve as biomarkers of disease severity and potential therapeutic targets. The anti-inflammatory profile of IL-33 (lower in crisis, higher in steady state) warrants further investigation as a protective factor. Given the limited therapeutic options in Sub-Saharan Africa (hematopoietic stem cell transplantation is largely unavailable), anti-inflammatory strategies targeting IL-1 family cytokines—such as anti-IL-1β antibodies, IL-1 receptor antagonists, or IL-18 binding protein—could offer new treatment avenues. Larger cohort studies are needed to validate these findings and establish cytokine-based risk stratification for complications like stroke in African SCD populations.

PICO

PPOPULATION

90 sickle cell disease patients (SSFA2, SFA2, SC genotypes) aged 4–55 years in Côte d'Ivoire

IINTERVENTION

Measurement of 13 plasma cytokines/chemokines (IL-1β, IL-18, IL-33, IL-6, IL-8, IL-10, TNFα, IFN-α2, IFN-γ, MCP-1, IL-12p70, IL-17A, IL-23) using BioLegend LEGENDplex Human Inflammation Panel

OOUTCOME

Cytokine levels (pg/ml) in plasma; association with clinical status (crisis vs. steady state), hemoglobin type, and complications (stroke, leg ulcer, osteonecrosis)

STUDY TYPE

case-control

SPECIALTY

hematology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10034065

Are IL-1 family cytokines important in management of sickle cell disease in Sub-Saharan Africa patients?

Frontiers in Immunology

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ABSTRACT

Abstract Introduction Sickle cell disease (SCD) is the most common genetic disease found in Africa and throughout the world. It is responsible for a high rate of hemolysis, systemic inflammation, and modulation of the immune system with the involvement of immunological molecules, such as cytokines. IL-1β is a major inflammatory cytokine. IL-18 and IL-33, members of IL-1 family, also exhibit characteristics of inflammation-related cytokines. Thus, in order to contribute to the evaluation of the severity and prognosis of SCD in Africa, this study aimed to estimate the cytokine response, in particular the levels of cytokines of the IL-1 family, in sickle cell patients living in a Sub-Saharan country. Methods Ninety patients with a diagnosis of SCD were recruited with different hemoglobin types. Samples were assessed for cytokine levels using the Human Inflammation Panel assay from BioLegend. The assay allows the simultaneous quantification of 13 human inflammatory cytokines/chemokines, i.e., IL-1β, IFN-α2, IFN-γ, TNFα, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33. Results and discussion the assessment of plasma cytokines in SCD patients revealed significantly increased levels of IL-1 family cytokines in crisis compared to steady state, suggesting a substantial involvement of these cytokines in clinical exacerbation. This suggests the possibility of a causal effect in the SCD pathology and can open the way to define better care, pointing toward new therapeutic avenues for sickle disease in Sub-Saharan Africa. Keywords: sickle cell disease, cytokines, IL-1, IL-18, IL-33, Africa, chemokines

CITATION EXPORT

Liliane K Siransy, Romuald S Dasse, Honoré Adou et al.. Are IL-1 family cytokines important in management of sickle cell disease in Sub-Saharan Africa patients?. Frontiers in Immunology. (2023). https://doi.org/10.3389/fimmu.2023.954054

AUTHORS

12 · 3 CENTRES

Liliane K Siransy, Romuald S Dasse, Honoré Adou, Patricia Kouacou, Sidonie Kouamenan, Yassongui Sekongo, Richard Yeboah, Charlene Memel, Aniella Assi-Sahoin, Salimata Y Moussa, Doris Oura, Jocelyne Seri

1 Immunology–Allergology Department, Medical Sciences, Felix Houphouet Boigny University, Abidjan, Côte d’Ivoire
2 Transfusional therapeutic department, National Blood Transfusion Center, Abidjan, Côte d’Ivoire
3 Immunology Department, CHU Bouake, Alassane Ouattara University, Bouake, Côte d’Ivoire