J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://jh.elmerpub.com

Original Article

Volume 14, Number 3, June 2025, pages 124-132

Inflammatory Cytokines in Association With High Fetal Hemoglobin Level Reduce the Episodes of Vaso-Occlusive Crisis in Sickle Cell Patients

↓ Figure 1. Association between cytokines and sickle cell disease patients in steady and crisis state, and healthy controls.

↓ **Table 1.** Demographic Data of All Participants
Variable	Total (N = 521)
Age
6 - 16 years	144 (27.63%)
17 - 27 years	153 (29.26%)
28 - 38 years	105 (20.15%)
39 - 49 years	68 (13.05%)
49 - 59 years	36 (6.90%)
59 - 65 years	15 (2.87%)
Mean age, years	26.69 ± 17.00
Male (N = 260)	260 (49.90%)
Female (N = 261)	261 (50.09%)

↓ Table 1. Demographic Data of All Participants

Variable

Total (N = 521)

Age

6 - 16 years

144 (27.63%)

17 - 27 years

153 (29.26%)

28 - 38 years

105 (20.15%)

39 - 49 years

68 (13.05%)

49 - 59 years

36 (6.90%)

59 - 65 years

15 (2.87%)

Mean age, years

26.69 ± 17.00

Male (N = 260)

260 (49.90%)

Female (N = 261)

261 (50.09%)

↓ **Table 2.** Hematological Profile of Sickle Cell Patients in Steady State and Crisis State, SCT Group, and Healthy Control Group
Hematological variables	Steady state (n = 180)	Crisis state (n = 96)	SCT (n = 117)	Healthy control (n = 128)	Crisis vs. steady state (Mann-Whitney z value)	Healthy control vs. crisis state (Mann-Whitney z value)	Healthy control vs. steady state (Mann-Whitney z value)	SCT vs. steady state (Mann-Whitney z value)	SCT vs. crisis state (Mann-Whitney z value)	Healthy control vs. SCT (Mann-Whitney z value)
P < 0.05, *P < 0.001. Hb F: fetal hemoglobin; Hb S: sickle hemoglobin; HCT: hematocrit; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; MCV: mean corpuscular volume; RBC: red blood cell; RDW: red cell distribution width; SCT: sickle cell trait; SD: standard deviation; THR: platelet/thrombocytes; WBC: white blood cell.
Age (years)	23.31 ± 14.83	25.16 ± 13.41	31.65 ± 17.65	27.08 ± 13.73
Male/female	96/84	49/47	54/63	61/67
WBC count (× 10⁹/L (mean ± SD)	8.47 ± 3.57	11.74 ± 7.48	8.11 ± 3.37	7.37 ± 2.46	-4.545**	-2.962*	-3.262*	-2.54*	-3.32*	-0.372
RBC count (× 10⁹/L) (mean ± SD)	3.51 ± 1.01	3.32 ± 1.12	4.59 ± 0.87	4.61 ± 1.03	-1.593	-7.495**	-9.024**	-10.07**	-8.36488**	-2.261*
MCV (fL) (mean ± SD)	88.73 ± 10.32	85.83 ± 12.98	81.46 ± 9.21	84.20 ± 9.34	-2.058*	-0.455	-3.636**	-4.705**	-1.662	-1.466
HCT (L/L) (mean ± SD)	30.60 ± 9.40	27.57 ± 8.96	34. ± 4.09	38.63 ± 9.29	-2.143*	-7.334**	-7.189**	-7.549**	-7.80**	-0.755
MCH (pg) (mean ± SD)	27.56 ± 5.03	29.05 ± 8.78	25.70 ± 5.14	26.90 ± 5.13	-0.400	-1.500	-1.427	-2.950*	-2.815*	-1.677
MCHC (g/dL) (mean ± SD)	30.85 ± 3.58	32.95 ± 4.47	31.00 ± 5.82	31.90 ± 4.19	-3.299*	-1.564	-1.679	-.0.312	-2.047*	-0.911
RDW (%) (mean ± SD)	16.00 ± 3.58	15.52 ± 5.74	15.30 ± 10.59	12.25 ± 2.22	-2.456*	-6.497**	-9.803**	-.0.8447**	-5.509**	-1.065
Hb (g/dL) (mean ± SD)	9.34 ± 1.87	8.85 ± 2.32	11.83 ± 1.87	12.36 ± 3.47	-1.159	-7.591**	-9.029**	-9.431**	-7.92**	-1.096
THR (mean ± SD)	236.92 ± 171.46	305.30 ± 192.21	211.15 ± 122.63	209.40 ± 107.60	-1.815	-1.166	-480	-0.430	-1.163	-0.164
Hb F (%) (mean ± SD)	20.02 ± 5.04	18.84 ± 6.31	1.28 ± 1.12	0.66 ± 0.45	-1.179*	-12.60**	-14.89**	-17.071**	-13.004**	-7.264**
Hb S (%) (mean ± SD)	71.91 ± 6.60	71.21 ± 8.09	31.54 ± 5.90	NA	-0.628	NA	NA	-16.64**	-13.004**	NA

↓ Table 2. Hematological Profile of Sickle Cell Patients in Steady State and Crisis State, SCT Group, and Healthy Control Group

Hematological variables

Steady state (n = 180)

Crisis state (n = 96)

SCT (n = 117)

Healthy control (n = 128)

Crisis vs. steady state (Mann-Whitney z value)

Healthy control vs. crisis state (Mann-Whitney z value)

Healthy control vs. steady state (Mann-Whitney z value)

SCT vs. steady state (Mann-Whitney z value)

SCT vs. crisis state (Mann-Whitney z value)

Healthy control vs. SCT (Mann-Whitney z value)

*P < 0.05, **P < 0.001. Hb F: fetal hemoglobin; Hb S: sickle hemoglobin; HCT: hematocrit; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; MCV: mean corpuscular volume; RBC: red blood cell; RDW: red cell distribution width; SCT: sickle cell trait; SD: standard deviation; THR: platelet/thrombocytes; WBC: white blood cell.

Age (years)

23.31 ± 14.83

25.16 ± 13.41

31.65 ± 17.65

27.08 ± 13.73

Male/female

96/84

49/47

54/63

61/67

WBC count (× 10⁹/L (mean ± SD)

8.47 ± 3.57

11.74 ± 7.48

8.11 ± 3.37

7.37 ± 2.46

-4.545**

-2.962*

-3.262*

-2.54*

-3.32*

-0.372

RBC count (× 10⁹/L) (mean ± SD)

3.51 ± 1.01

3.32 ± 1.12

4.59 ± 0.87

4.61 ± 1.03

-1.593

-7.495**

-9.024**

-10.07**

-8.36488**

-2.261*

MCV (fL) (mean ± SD)

88.73 ± 10.32

85.83 ± 12.98

81.46 ± 9.21

84.20 ± 9.34

-2.058*

-0.455

-3.636**

-4.705**

-1.662

-1.466

HCT (L/L) (mean ± SD)

30.60 ± 9.40

27.57 ± 8.96

34. ± 4.09

38.63 ± 9.29

-2.143*

-7.334**

-7.189**

-7.549**

-7.80**

-0.755

MCH (pg) (mean ± SD)

27.56 ± 5.03

29.05 ± 8.78

25.70 ± 5.14

26.90 ± 5.13

-0.400

-1.500

-1.427

-2.950*

-2.815*

-1.677

MCHC (g/dL) (mean ± SD)

30.85 ± 3.58

32.95 ± 4.47

31.00 ± 5.82

31.90 ± 4.19

-3.299*

-1.564

-1.679

-.0.312

-2.047*

-0.911

RDW (%) (mean ± SD)

16.00 ± 3.58

15.52 ± 5.74

15.30 ± 10.59

12.25 ± 2.22

-2.456*

-6.497**

-9.803**

-.0.8447**

-5.509**

-1.065

Hb (g/dL) (mean ± SD)

9.34 ± 1.87

8.85 ± 2.32

11.83 ± 1.87

12.36 ± 3.47

-1.159

-7.591**

-9.029**

-9.431**

-7.92**

-1.096

THR (mean ± SD)

236.92 ± 171.46

305.30 ± 192.21

211.15 ± 122.63

209.40 ± 107.60

-1.815

-1.166

-480

-0.430

-1.163

-0.164

Hb F (%) (mean ± SD)

20.02 ± 5.04

18.84 ± 6.31

1.28 ± 1.12

0.66 ± 0.45

-1.179*

-12.60**

-14.89**

-17.071**

-13.004**

-7.264**

Hb S (%) (mean ± SD)

71.91 ± 6.60

71.21 ± 8.09

31.54 ± 5.90

-0.628

-16.64**

-13.004**

↓ **Table 3.** Logistic Regression Models Showing Interaction Between Hb F and Cytokines IL-17, IL-10, and IL-β in Crisis and Steady SCD Patients
Cytokine	Coefficient	Standard error	Lower 95% confidence interval	Upper 95% confidence interval	Odds ratio	P value
Significant association *P < 0.05. Hb F: fetal hemoglobin; IL: interleukin; SCD: sickle cell disease.
Hb F	-0.050193	0.032364	-0.113625	0.0132385	0.951046	0.121
Model 1
Hb F	-0.130237	0.051297	-0.2307774	-0.0296959	0.877888	0.011*
IL-17	0.0060895	0.00994	-0.013393	0.025572	1.006108	0.54
Model 2
Hb F	-0.132508	0.052174	-0.2347672	-0.0302486	0.875896	0.011*
IL-10	0.0003799	0.007235	-0.0138011	0.014561	1.00038	0.958
Model 3
Hb F	-0.130346	0.053042	-0.234307	-0.0263852	0.877792	0.014*
IL-β	0.0491697	0.063141	-0.0745843	0.1729238	1.050399	0.436

↓ Table 3. Logistic Regression Models Showing Interaction Between Hb F and Cytokines IL-17, IL-10, and IL-β in Crisis and Steady SCD Patients

Cytokine

Coefficient

Standard error

Lower 95% confidence interval

Upper 95% confidence interval

Odds ratio

P value

Significant association *P < 0.05. Hb F: fetal hemoglobin; IL: interleukin; SCD: sickle cell disease.

Hb F

-0.050193

0.032364

-0.113625

0.0132385

0.951046

0.121

Model 1

Hb F

-0.130237

0.051297

-0.2307774

-0.0296959

0.877888

0.011*

IL-17

0.0060895

0.00994

-0.013393

0.025572

1.006108

0.54

Model 2

Hb F

-0.132508

0.052174

-0.2347672

-0.0302486

0.875896

0.011*

IL-10

0.0003799

0.007235

-0.0138011

0.014561

1.00038

0.958

Model 3

Hb F

-0.130346

0.053042

-0.234307

-0.0263852

0.877792

0.014*

IL-β

0.0491697

0.063141

-0.0745843

0.1729238

1.050399

0.436

↓ **Table 4.** Logistic Regression Analysis of Cytokines, Hb F Level With Crisis and Steady SCD Patients
Cytokine	Coefficient	Standard error	Lower 95% confidence interval	Upper 95% confidence interval	Odds ratio	P value
Hb F: fetal hemoglobin; IFN: interferon; IL: interleukin; SCD: sickle cell disease; TNF: tumor necrosis factor.
IL-6	0.0065854	0.003496	-0.0002658	0.0134366	1.006607	0.06
IL-17	0.0076512	0.009619	-0.011201	0.0265035	1.007681	0.426
IL-8	0.0001269	0.00043	-0.0007164	0.0009702	1.000127	0.768
TNF-α	0.002244	0.001758	-0.0012016	0.0056897	1.002247	0.202
IFN-γ	-0.002933	0.009023	-0.026165	0.0147509	0.997072	0.745
IL-10	-0.00375	0.006572	-0.0166307	0.0091312	0.996273	0.568
IL-1β	0.0806308	0.068892	-0.0543955	0.2156572	1.083971	0.242
Hb F	-0.050193	0.032364	-0.113625	0.0132385	0.951046	0.121

↓ Table 4. Logistic Regression Analysis of Cytokines, Hb F Level With Crisis and Steady SCD Patients

Cytokine

Coefficient

Standard error

Lower 95% confidence interval

Upper 95% confidence interval

Odds ratio

P value

Hb F: fetal hemoglobin; IFN: interferon; IL: interleukin; SCD: sickle cell disease; TNF: tumor necrosis factor.

IL-6

0.0065854

0.003496

-0.0002658

0.0134366

1.006607

0.06

IL-17

0.0076512

0.009619

-0.011201

0.0265035

1.007681

0.426

IL-8

0.0001269

0.00043

-0.0007164

0.0009702

1.000127

0.768

TNF-α

0.002244

0.001758

-0.0012016

0.0056897

1.002247

0.202

IFN-γ

-0.002933

0.009023

-0.026165

0.0147509

0.997072

0.745

IL-10

-0.00375

0.006572

-0.0166307

0.0091312

0.996273

0.568

IL-1β

0.0806308

0.068892

-0.0543955

0.2156572

1.083971

0.242

Hb F

-0.050193

0.032364

-0.113625

0.0132385

0.951046

0.121