Research Article

Clinical Immunology & Research

Th1 and Th2 Cytokines Pattern among Sickle Cell Disease Patients in Côte
d’ivoire
Liliane K. Siransy1*, Chiayé C.A. Yapo-Crézoit2, Maxime K. Diane3, Sidonie Goore3, Saydou Kaboré3,
Bettina Koffi-Kabran3 and Seidou Konaté3
1
Félix Houphouet Boigny University- Medical Sciences
-Immunology –Allergology Department, 1, boulevard de *
Correspondence:
l’Université, Cocody, BP V 34 Abidjan-Côte d’Ivoire. Liliane Kouabla Siransy, Félix Houphouet Boigny University-
Medical Sciences -Immunology –Allergology department, 1,
2
Pasteur Institute of Côte d’Ivoire, Biology of Immunity boulevard de l’Université, Cocody, Abidjan-Côte d’Ivoire, Tel:
department Cocody, 01 BP 490 Abidjan-Côte d’Ivoire. +22567650761; Fax: +225 21358060; E-mail: [email protected].
3
National Blood Transfusion Center, Therapeutic and Research Received: 13 January 2018; Accepted: 16 February 2018
unit 52, boulevard de Marseille, Zone 3, BP V 15 Abidjan-Côte
d’Ivoire.

Citation: Liliane K. Siransy, Chiayé C.A. Yapo-Crézoit, Maxime K. Diane, et al. Th1 and Th2 Cytokines Pattern among Sickle Cell
Disease Patients in Côte d’ivoire. Clin Immunol Res. 2018; 2(1): 1-4.

ABSTRACT
Introduction: Sickle cell disease (SCD) is the most prevalent genetic disease worldwide and particularly
reaches its highest prevalence in sub-Saharan African countries. In Côte d’Ivoire, the SCD prevalence rate is
12%. Many evidences show that the immune system plays an important role in this inflammatory condition with
secreting inflammatory cytokines.

This work attempts to identify the cytokine pattern displayed by Ivorian patients during the course of disease, as
Th1 cytokines, as well as Th2 cytokines. Furthermore, this study desires to contribute to identify advantages of
chronic transfusion in SCD patients.

Patients and Methods: 49 subjects (4 to 55 years) were prospectively enrolled in the study after an informed
consent. The patients were assigned in 2 groups, patients in steady state and patients in crisis. Serums were
measured in San Diego Biolegend laboratory by using LEGENDplexTM Human Inflammation Panel assays
and ELISA.

Results: Evaluation of serum cytokines in SCD crisis patients revealed an increased level for IL-1β, IL-6 and
IL-10 cytokines. The IFN-γ to IL-4 ratio was 1.92 in crisis subjects and 3.55 in steady state subjects indicating
a trend toward a Th2 bias in crisis patients.

Conclusion: The role of cytokines in role in pathogenesis and progression in SCD is well established. However,
accurate data are lacking for people with SCD in Sub-Saharan Africa where the disease is endemic. This study
reveals a Th2 bias in SCD patients. The reduction in cytokine levels observed in our transfused patients provides
an overview of the definite benefit of chronic transfusion.

Keywords the prevalence varies between 20% and 30% [1,2]. In Côte d’Ivoire,
Th1-Th2 balance, Cytokines, Africa, Sickle cell disease. the SCD prevalence rate is 12 % [3]. As such, SCD is one of the
greatest public health treat and represent a public health problem.
Introduction Sickle cell disease (SCD) is in fact a chronic inflammatory disease
Sickle cell disease (SCD) is the most prevalent genetic disease and the permanently activated immunoinflammatory status exhibit
worldwide and particularly reaches its highest prevalence in sub- increased levels of proinflammatory cytokines with chronic
Saharan African countries. Particularly in areas around the equator, hemolysis, frequent infections, recurrent clinical and subclinical
Clin Immunol Res, 2018 Volume 2 | Issue 1 | 1 of 6
occlusion of microcirculation and result in tissue injury, chronic Steady-state SCD control patients were matched with crisis SCD
organ damage and failure and ultimately, premature death [4,5]. patients according to sex, gender, hemoglobin type, hemoglobin
Classically two clinical profiles are well known, sickle cell steady level, body mass index (BMI) and chronic transfusion. All subjects
state and sickle cell crisis. The steady state is a period during which were coming most from Côte d’Ivoire and West African countries
the patient feels well but it‘s a precarious situation which can (Nigeria, Togo, Ghana, Mali, and Guinea).
degenerate into the second profile, the vasoocclusive crisis, at any
time [6]. The mechanisms by which sickle cell crisis are initiated Cytokines assays
are complex and multifactorial and involves many factors such as Blood sample were collected by veinopuncture in EDTA for the
cytokines [6,7]. Many evidences show that both type I and type determination of the basic hematological indices and for the cytokine
II cytokines are significantly altered in SCD patients. CD4+ and assay. Complete blood counts were obtained with an electronic
CD8+ cells are further divided into subsets by their function and cell counter (Sysmex XN 550 Hematology analyzer). The plasma
pattern of cytokine secretion. Type 1 (Th1) cells typically produce was separated from the tube sample at 1,000g at 4°C for 10 min,
IL-2, tumor necrosis factor- β (TNF- β) and interferon α(IFN α), aliquoted and stored at -30°C for cytokine assays. Prior to use, the
while type 2 (Th2) cells produce IL-4, IL-5, IL-6, IL-9 and IL- samples were thawed completely, mixed and centrifuged. Serums
10 . A predominance of Th1 cytokines results in the induction of were measured by using BioLegend’s LEGENDplexTM Human
vigorous mediated immunity while a predominant Th2-biased Inflammation Panel assays which is bead-based immunoassays,
response results in stronger humoral immunity [8]. using fluorescence encoded beads and The BioLegend LEGEND
MAX™ Human IL-4 ELISA Kit. These panels allow simultaneous
While there are published reports of individual cytokines in quantification of many human inflammatory cytokines and
sickle cell disease patients, few studies are really investigating chemokines, but we had focused on Th1 cytokines (IFN γ, IL-1β,
the relative levels of Th1-type and Th2-type cytokines in black TNF α, IL-12 p70) and Th2 cytokines (IL-4, IL-6, IL-10). The
Africans. This work attempts to identify the cytokine pattern assay was performing using ELISA for IL-4 and a filter plate for
displayed by these patients during the course of disease, as Th1 the others cytokines in Biolegend laboratory in San Diego, US. A
cytokines, such as TNF α, IL-1 β, IL-12p70 and IFNγ, as well as minimum of 3000 positive beads for these cytokines was acquired
Th2 cytokines, such as IL-4, IL-6 and IL-10. Furthermore, this with a cytometer type BD FACSCalibur™. The BioLegend
study desires to contribute to identify factors that can help for a LEGEND MAX™ Human IL-4 ELISA Kit, Sandwich Enzyme-
better comprehension of the physiopathology and therapeutics of Linked Immunosorbent Assay (ELISA) with a 96-well strip plate
the disease. that is pre-coated with a capture antibody was used to detect
IL-4. All samples were run and analyzed on the same day after
Patients and Methods being thawed completely. Manufactured supplied controls were
Study population used to monitor coefficients of variation, which were <10%. The
This is a prospective study with 49 SCD patients from 4 to 55 minimum detectable concentration for Th1 and Th2 cytokines
years old followed at the transfusion therapeutic unit located in were respectively IFN γ: 1.5pg/ml, IL-1β: 0.9pg/ml, TNF α: 1.0
National blood Transfusion Center in Abidjan, Côte d’Ivoire. It pg/ml, IL-12 p70: 0.6pg/ml, IL-4: 0.6 pg/ml, IL-6: 1pg/ml, IL-10:
was conducted between from October 2016 to February 2017 after 0.8pg/ml. Data analysis was done using LEGENDplexTM Data
approval from the national ethics board and informed consent was Analysis Software when data acquisition is completed.
obtained from the patients’ parents.
Statistical analysis
Each subject was prospectively enrolled in the study after an All results are expressed as mean+/- SD. Data were analyzed using
informed consent was obtained. Patients were assigned in 2 groups: the SPSS, version 15, for Windows. Statistical significance was
patients in steady state (no acute illness, no crisis or infection calculated using Student’s unpaired t test, the Mann-Witney U test,
during the previous 3 months) for the first group and patients Chi-square and Fisher’s exact test. Statistical test results with a P
admitted for anemia, infection, and crisis for the second group. value ≤0.05 were considered to be significant.

Documentation of homozygous or heterogynous sickle cell patients Results

had been determined by hemoglobin electrophoresis on cellulose Demographic characteristics in the sickle cell patients
acetate strips (PH 9.2). The vaso-occlusive crisis (VOC) patients Fourty nine patients with a diagnosis of sickle cell disease (SCD),
were admitted to the unit and those who were non-symptomatic, comprising 26 males (53.06%) and 23 females (46.94 %), were
steady state sickle cell patients coming at the unit for routine recruited.
check-ups.
The mean age for all SCD patients were respectively, 27.82 ±
Vaso-occlusive crisis (VOC) was defined as an episode of diffuse 13.77 years (min/max= 4/50 years) for crisis group and 20 ± 13.74
acute pain occurring in the abdomen, back, chest, bone, joint, or (min/max= 4/55 years) for the steady state group. There was no
multiple sites of pain, necessitating hospital admission and or significant difference in the age range between group 1 and group
analgesic administration. Clinical investigations were assessed by 2 (p value= 0.09) and the sex ratio was 1 and 1.3 (in favor of men)
hematology specialist. respectively in group 1 and 2 (Table 1).
Clin Immunol Res, 2018 Volume 2 | Issue 1 | 2 of 6
 Parameters % Crisis Steady state p value in steady state subjects were respectively 7.27 ± 11.30 pg/ml, 2.10
Sex ratio (men/female) 1,0 1,3 ± 4.46 pg/ml , 7.05 ± 12.26 pg/ml, 1.30 ± 2.14 pg/ml. There were
no significant differences in the 2 groups (Table 2).
27,82 ± 13,77 20 ± 13,74
Age (years) 0,09
(4-55) (4-50)
Transfusion program % 19,2 45 0,03 Crisis Steady state p value
20,89 ± 3,12 19, 90 ± 5,14 IFN-γ 6.64 ± 8.20 7,27 ±11,30 0,8
BMI (body mass index) 0,4
(13,67-26,15) (7,56-27,34) TH1 TNF-α 4,05 ± 9,73 2,10± 4,46 0,2
SSFA2 53,06 57,14 47,62 cytokines IL-1β 41,65 ± 183,26 7,05 ± 12,26 0,3
Type SFA2 24,49 28,57 19,05 IL-12p70 4,23 ± 9,14 1,30 ± 2,14 0,1
0,72
hemoglobin SC 16,33 7,14 28,57 IL-4 3,45 ±6,07 2,05 ±1,65 0,4
AFA2 6,12 7,14 4,76 TH2
IL-6 50,52 ± 113.32 83,51 ± 198,64 0,3
cytokines
A+ 20,41 20,00 21,05 IL10 13,45 ±22,18 6,45 ±7,94 0,1
B+ 14,29 20,00 5,26 TH1/TH2 IFN-γ/IL-4 1.92 3,55
Blood group
O+ 46,94 46,67 47,37 0,29 balance TNF-α/IL-6 0,08 0,03
ABO %
AB+ 10,2 10,00 10,53 Table 2: Levels of cytokines in SCD patients.
O- 8,16 3,33 15,79
ccdeek 6,12 0 14,29 The data in table 2 show also the levels of IL-4, IL-6 and IL-10
ccDeek 65,31 64,29 66,67 (Th2 cytokines) in the sera of patients with crisis compared to
ccDEek 6,12 10,71 0
those in steady-state. The mean level of these Th2 cytokines in the
RH sera of crisis subjects were respectively 3.45 ± 6.07 pg/ml , 50.52
phenotype ccDeeK+ 2,04 3,57 0 0,06
% ± 113.32 pg/ml, 13.45 ± 22.18 pg/ml, while levels in steady state
CcDeek 16,33 14,29 19,05
subjects were respectively 2.05 ± 1.65 pg/ml, 83.51 ± 198.64 pg/
CcDEek 2,04 3,57 0
ml , 6.45 ± 7.94 pg/ml. There were no significant differences in the
Ccdeek 2,04 3,57 0 2 groups (Table 2).
8,09 ± 1,79 9,44 ± 2,40
Haemoglobin(g/l) 0,03
(4,8-12,50) (5,6-14,30)
Chronic transfusion was done in 45% of patients in steady state
Table 1: Demographics characteristics of SCD patients in Côte d'Ivoire. versus 19.2% in crisis patients (p=0.03). According to their
belonging to chronic transfusion program, the mean level of IL1β
Of the SCD patients, 21 (42.86 %) were in steady state and and IL-6 was lower in patients receiving chronic transfusion. (8.16
represented our stable controls (group 1), while 28 (57.14%) were
± 12.78pg/ml versus 33.55 ± 161.78pg/ml for IL1β and 28.15 ±
in crisis (group 2). Regarding hemoglobin type, 24 were HbSS
38.16pg/ml versus 78.35 ± 179.37pg/ml). No significant variation
homozygous type (53.06%), 14 were Sβ+ Thal heterozygous
was noted (Table 3).
type (24.49%), 8 HbSC (16.33%) and 3 βThal homozygous type
(6.12%).
Chronic transfusion program

The patients were phenotyped in ABO and Rh Kell. In ABO Yes (n=12) No (n=37) p value
system, the frequency of blood group were as followed: A Rh D IFN-γ 8,53 ± 10,04 6,07 ± 9,37 0,4
(20.41%), B Rh D ((14.29%), O Rh D (46.94%), AB Rh D (10.2%), TH1 TNF-α 2,39 ± 4,80 3,44 ± 8,78 0,6
O Rh D negative (8.16%) (Table1). In Rh Kell system, the ccDeeK cytokines IL-1β 8,16 ± 12,78 33,55 ± 161,78 0,5
phenotype was the most prevalent in both two groups (66.67% for IL-12p70 1,75 ± 2,93 3,37 ± 8,1 0,4
group 1 and 64.29% for group 2). IL-4 2,8 ± 3,00 3,11 ± 5,19 0,6
Th2
IL-6 28,15 ± 38,16 78,35 ± 179,37 0,1
Sickle cell disease was associated with lower level of hemoglobin cytokines
IL10 12,78 ± 16,10 9,32 ± 18,28 0,6
in steady state and crisis group (respectively 9.44 ± 2.40 and 8.09
± 1.79 g/l), showing a significant variation (p=0.03). Balance IFN-γ/IL-4 3,05 1,95
TH1/TH2 TNF-α/IL-6 0,08 0,04
Plasma levels of cytokines Table 3: Levels of cytokines in SCD patients according to chronic
The median concentrations for Th1 and Th2 cytokines measured transfusion program.
are shown in Table 2.
TH1/TH2 balance
The data in table 2 show the levels of IFN-γ, TNF a, Il-1β and IL- We calculated the ratios of the Th1 to Th2 cytokines in the plasma
12 p70 (Th1 cytokines) in the sera of patients with crisis compared in view of the fact that the ratios of Th1 to Th2 cytokines are more
to those in steady-state. The mean level of these Th1 cytokines in relevant and pertinent than the levels of these cytokines alone.
the sera of crisis subjects were respectively 6.64 ± 8.20 pg/ml, 4.05
± 9.73 pg/ml, 41.65 ± 183.26 pg/ml, 4.23 ± 9.14 pg/ml while levels The IFN-γ to IL-4 ratio is 1.92 in crisis subjects and 3. 55 in steady
Clin Immunol Res, 2018 Volume 2 | Issue 1 | 3 of 6
state subjects indicating a trend toward a Th2 bias in crisis patients B cells, and even antigen-presenting cells [16]. Recently, the
(Table 2). The TNF a to IL-6 ratio is 0.08 in crisis compared to involvement of IL-12, in inflammatory responses in SCA patients
0.03 in steady state patients and show also a Th2 bias in crisis has been described and thus appears to be the main cytokine
patients. that regulates Th1 differentiation [10,17,18]. In addition, IL-12
antagonizes Th2 differentiation and the production of IL-4 and is
Discussion inhibited by IL-10 [10].
Studies of cellular immunity and humoral factors have yielded
conflicting results in sickle cell disease. Furthermore, most reports Levels of IL-4 are low in steady-state (2.05 ± 1.65pg/ml) and crisis
of the roles and pattern of cytokines have focused mainly on non (3.45 ± 6.07pg/ml) SCD patients in this study and did not differ
African patients. In this study, we want to give our contribution significantly (p=0.4). The role of IL-4 is controversial. While some
on how the immune system plays an important role in SCD studies have reported that IL-4 levels increase during VOC, other
in Ivorians patients. Many evidences show that the chronic studies have demonstrated that IL-4 levels are higher during the
inflammatory state characterizes this disease, in both crisis and steady-state [8,19]. An investigation of the Th2 cytokine revealed
steady state conditions. In addition to an activated endothelium that plasma IL-4 levels were significantly higher among steady-
and leukocytosis, the inflammatory phenotype of sickle cell disease state HbSS patients than HbAA and HbAS individuals and may
is further characterized by rise levels of acute phase proteins differ between children in developed countries and children in
and cytokines [9]. Several cell types secrete pro-inflammatory developing countries [20] due to undernutrition.
cytokines that contribute to the occurrence of common cyclical
events in SCD patients [10]. In our SCD patients, a trend toward higher IL-10 levels in
patients in crisis than in steady state was found with no significant
Plasma levels of some Th1 and Th2 cytokines were evaluated in variation. Conflicting reports are reported on the role of IL-10 in
SCD steady state and crisis groups in order to estimate the role SCD patients. Sarray [21] demonstrated that changes in IL-10
of these cytokines in SCD and the inflammatory profile of the serum levels is predicting VOC in SCD patients and his results
patients. clearly demonstrated a significant association between reduced IL-
10 levels and the development of VOC and its severity. Patients
Evaluation of serum cytokines in SCD crisis patients in the present undergoing Hydroxyurea therapy had high levels of IL-10 [10]. IL-
study revealed an increased level for IL-1β and IL-10 cytokines 10 has a protective effect against the occurrence of severe malaria
in crisis group. IL-6 was higher in steady state group (83.51pg/ml in patients with sickle cell trait and confirm the contribution of this
versus 50.52pg/ml) with no significant variation and only IL-6 was cytokine to the regulation cellular iron status [10].
higher in this group (Table 2).
Th1-type cytokines activate anti-microbial functions in phagocytes
In a similar study [11] detectable levels of IL-1β ( crisis: 3.26 pg/ which determine protection against intracellular bacteria and
ml; steady state: 3.19 pg/ml) and IL-6 (crisis :14.18 pg/ml, steady protozoa while Th2-type cytokines, activate B cells and induce
state: 6.78 pg/ml) were found in the serum of patients in the antibody production, a function that is vital to the neutralisation
steady-state condition and crisis although this was not statistically of microbial toxins and certain viruses. The ratios of Th1 to
significant. Th2 cytokines are more relevant and pertinent than the levels of
these cytokines alone. As IFN-γ inhibits the expression of Th2
On the other hand, other authors showed that the mean serum cytokines such as IL- 4, and vice versa, the IFN- γ /IL-4 cytokine
IL-1β and IL-6 were respectively and significantly increased in ratio is considered to be a simple and direct indicator of Th1/Th2
the both group steady state (44.36 pg/ml/137.62 pg/ml) and crisis balance. The IFNγ to IL-4 ratio in plasma indicates a Th2 bias in
(42.59 pg/ml/175.7 pg/ml) [6]. Thus, contradictory findings are SCD patients [8,20]. Our observations support the same trend by
reported by multiples studies and may be due to the low number showing a Th2 pattern.
of SCD patients, the selection criteria and SCD phenotype and
genetic polymorphism of the cytokine [11-14]. With advances now reducing the side effects of transfusion over
the last decade clearly defining the efficacy for decreasing sickle
No significant detectable levels of IFNγ, TNFα, and IL-12p70 cell morbidity, the indications for transfusion have increased
were found in the sera of either group of patients although a slight [22,23]. Chronic transfusion lead to a significant improvement
increase was noted for TNFα and IL-12 in crisis group. Others in quality of life and is indicated for the prevention of primary
authors show higher levels in both groups [12,13,15]. and secondary stroke, acute cerebrovascular accidents and severe
acute chest syndrome. A way to decrease HbS level without
In our study, detectable levels of IL-12 were observed in crisis raising hematocrit is to associate phlebotomy and transfusion,
without significant difference as shown by Taylor et al. [16]. IL- which defines exchange transfusion. Patients receive RBC
12 is composed of p35 and p40 subunits, which, when combined transfusions via simple transfusion, partial exchange transfusion or
together form the bioactive IL-12p70 [17]. IL-12 is predominantly erythrocytapheresis, every 4-5 weeks, depending on quantitative
proinflammatory and prostimulatory cytokines and a major hemoglobin S concentration. It may be performed manually,
function is the induction of IFN-γ produced by NK cells, T cells, exchanging patient’s whole blood with packed red cells, or using a
Clin Immunol Res, 2018 Volume 2 | Issue 1 | 4 of 6
cell separator, with reinfusion of the patient’s plasma [24]. References
1. Diallo D, Tchernia G. Sickle cell disease in Africa. Curr Opin
In our study, Th1 and Th2 cytokines levels were lower in chronic Hematol. mars 2002; 9: 111-116.
transfused patients compared to non transfused SCD patients but 2. Williams TN. Sickle Cell Disease in Sub-Saharan Africa.
the variation was not significant (Table 3). Leukocyte-reduced units Hematol Oncol Clin North Am Avr. 2016; 30: 343-358.
have beneficial effects in reducing alloimmunization, transfusion 3. Le Gallais D, Lonsdorfer J, Fabritius H, et al. Prevalence of
reactions, platelet refractoriness, and infection transmission [25] the sickle cell trait among students in a physical education
but in our area, they are little used because of lack of materials. college in Côte-d’Ivoire. Nouv Rev Fr Hematol. 1989; 31:
The low levels of cytokines in our SCD patients should offers 409-412.
insight into the mechanism of the protective effect of transfusion 4. Akohoue SA, Shankar S, Milne GL, et al. Energy expenditure,
[26]. inflammation, and oxidative stress in steady-state adolescents
with sickle cell anemia. Pediatr Res. Févr. 2007; 61: 233-238.
Patients who are compliant with blood transfusion are rarely 5. Bandeira ICJ, Rocha LBS, Barbosa MC, et al. Chronic
hospitalized for painful crises [22]. Kalechman demonstrate in inflammatory state in sickle cell anemia patients is associated
his study that 2 weeks after blood transfusion, a sharp decrease with HBBS haplotype. Cytokine. Févr. 2014; 65: 217-221.
was observed in the generation of some cytokines. A decrease 6. Pathare A, Kindi SA, Daar S, et al. Cytokines in sickle cell
of about 70% was observed in interleukin-2, tumor necrosis disease. Hematol Amst Neth. Oct. 2003; 8: 329-337.
factor, and gamma-interferon secretion. Actually, apheresis can 7. Makis AC, Hatzimichael EC, Bourantas KL. The role of
remove pathogens and mediators that contribute to pathogenic cytokines in sickle cell disease. Ann Hematol. Août. 2000; 79:
inflammatory responses in diseases and should be introduced in 407-413.
local management of our patients [27]. 8. Raghupathy R, Haider MZ, Azizieh F, et al. Th1 and Th2
cytokine profiles in sickle cell disease. Acta Haematol. 2000;
Our study has some limitations. First, the results are based on 103: 197-202.
data from small number of samples and a multi-center study was 9. Olenscki Gilli SC, Pericole FV, Benites BD, et al. Cytokine
required to be performed to validate the results. Second, a small polymorphisms in sickle cell disease and the relationship with
increase in circulating cytokine levels may reflect a significant cytokine expression. Exp Hematol. Juill. 2016; 44: 583-589.
increase in cytokine concentration at the tissue level. As Tam et 10. Pitanga TN, Vilas-Boas W, Cerqueira BAV, et al. Cytokine
al. [28], the systemic measures in our study may underestimate profiles in sickle cell anemia: Pathways to be unraveled. Adv
the concentrations at a local level. Therefore our results should Biosci Biotechnol. 3 juill. 2013; 04: 6.
also be interpreted with finesse and further studies should take in 11. Keikhaei B, Mohseni AR, Norouzirad R, et al. Altered levels
consideration both local and systemic aspects. Third, In Africa and of pro inflammatory cytokines in sickle cell disease patients
particularly, in Ivory Coast, undernutrition is prevalent. 15-20% of during vaso occlusive crises and the steady state condition.
the population suffers from Under nutrition. In general, this figure is Eur Cytokine Netw. Mars. 2013; 24: 45-52.
associated with poor immune function and is consequently regarded 12. Pathare A, Al Kindi S, Alnaqdy AA, et al. Cytokine profile of
as the most common cause of immunodeficiency worldwide [29]. sickle cell disease in Oman. Am J Hematol. 2004; 77: 323-
This may have strong impact on cytokine secretion. 328.
13. Sarray S, Saleh LR, Lisa Saldanha F, et al. Serum IL-6, IL-10,
Conclusion and TNFα levels in pediatric sickle cell disease patients during
The present study demonstrates a Th2 driven immune response vasoocclusive crisis and steady state condition. Cytokine.
SCD patients. Understanding the roles of different cytokines in Mars. 2015; 72: 43-47.
the pathology of SCD is essential for the development of effective 14. Vicari P, Adegoke SA, Mazzotti DR, et al. Interleukin-1β
therapies for this disease. The reduction in cytokine levels observed and interleukin-6 gene polymorphisms are associated with
in our transfused patients provides an overview of the definite manifestations of sickle cell anemia. Blood Cells Mol Dis.
benefit of chronic transfusion but apheresis in this area is still little Mars. 2015; 54: 244-249.
used and even absent in transfusion protocols. Research including 15. Ojo OT, Shokunbi WA, Ibijola AA, et al. Serum Levels of
more subjects and more research should be carried out in the future Gamma-interferon and Interleukin-4 in Homozygous Sickle
for further exploring and reducing morbidity and mortality. Cell Anaemia Patients. Int Blood Res Rev. avr. 2016; 5: 1-7.
16. Taylor SC, Shacks SJ, Qu Z. In vivo production of type 1
Acknowledgment cytokines in healthy sickle cell disease patients. J Natl Med
We appreciate the hands on training, the excellent technical Assoc. nov. 1999; 91: 619-624.
assistance and the donation of reagents by Shi Shaoquan and 17. Gee K, Guzzo C, Che Mat NF, et al. The IL-12 family
Sun Biggang and in Biolegend, in San Diego. The authors thank of cytokines in infection, inflammation and autoimmune
Kady Kassogue for help with obtaining patient consents, patient disorders. Inflamm Allergy Drug Targets. Mars. 2009; 8: 40-
transfusion data and blood sample and dr Aholi for his help in the 52.
statistical analysis of the data. 18. Vignali DAA, Kuchroo VK. IL-12 Family Cytokines:
Clin Immunol Res, 2018 Volume 2 | Issue 1 | 5 of 6
 Immunological Playmakers. Nat Immunol. 2012; 13: 722- of chronic transfusion therapy. Am J Hematol. 2004; 76: 57-
728. 60.
19. Musa BOP, Onyemelukwe GC, Hambolu JO, et al. Pattern 24. Montalembert M de. Échanges érythrocytaires chez les
of serum cytokine expression and T-cell subsets in sickle patients drépanocytaires. Hématologie. 2007; 13: 243-249.
cell disease patients in vaso occlusive crisis. Clin Vaccine 25. Vichinsky EP. Current issues with blood transfusions in sickle
Immunol CVI. Avr. 2010; 17: 602-608. cell disease. Semin Hematol. 2001; 38: 14-22.
20. Knight-Madden J, Vergani D, Patey R, et al. Cytokine 26. Kalechman Y, Gafter U, Sobelman D, et al. The effect of a
levels and profiles in children related to sickle cell disease single whole blood transfusion on cytokine secretion. J Clin
and asthma status. J Interferon Cytokine Res Off J Int Soc Immunol. Mars. 1990; 10: 99-105.
Interferon Cytokine Res. 2012; 32: 1-5. 27. Sloan SR, Andrzejewski C, Aqui NA, et al. Role of therapeutic
21. Sarray S, Almawi WY. Contribution of Reduced Interleukin-10 apheresis in infectious and inflammatory diseases: Current
Levels to the Pathogenesis of Osteomyelitis in Children with knowledge and unanswered questions. J Clin Apheresis.
Sickle Cell Disease. Clin Vaccine Immunol CVI. 2015; 22: 2015; 30: 259-264.
1020-1024. 28. Tam CS, Garnett SP, Cowell CT, et al. IL-6, IL-8 and IL-10
22. Master S, Ong M, Mansour RP. Blood Transfusion in levels in healthy weight and overweight children. Horm Res
Adult Patients with Sickle Cell Disease: Incidence of Paediatr. 2010; 73: 128-134.
Alloimmunization. Blood. 2 déc. 2016; 128: 4859. 29. van Wesenbeeck CF, Keyzer MA, Nubé M. Estimation of
23. Sakhalkar VS, Rao SP, Weedon J, et al. Elevated plasma undernutrition and mean calorie intake in Africa: methodology,
sVCAM-1 levels in children with sickle cell disease: Impact findings and implications. Int J Health Geogr. 2009; 8: 37.

© 2018 Liliane K. Siransy, et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License

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