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. 2010 Apr;17(4):602-8.
doi: 10.1128/CVI.00145-09. Epub 2010 Feb 3.

Pattern of serum cytokine expression and T-cell subsets in sickle cell disease patients in vaso-occlusive crisis

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Pattern of serum cytokine expression and T-cell subsets in sickle cell disease patients in vaso-occlusive crisis

Bolanle O P Musa et al. Clin Vaccine Immunol. 2010 Apr.

Abstract

The pathogenesis of sickle vaso-occlusive crisis (VOC) in sickle cell disease (SCD) patients involves the accumulation of rigid sickle cells and the stimulation of an ongoing inflammatory response, as well as the stress of infections. The immune response, via cytokine imbalances and deregulated T-cell subsets, also has been proposed to contribute to the development of VOC. In this study, a panel of high-sensitivity cytokine kits was used to investigate cytokines in the sera of SCD patients in VOC. The results were compared primarily with those for stable SCD patients and secondarily with those for normal healthy people who served as controls. The cytokines studied included interleukin-2 (IL-2), IL-4, and IL-10. Lymphocyte subsets of patients with VOC were also studied and were compared with those of both control groups (20 stable patients without crisis [SCD group] and 20 normal healthy controls [NHC]). The VOC group was notable for remarkably elevated levels of IL-4, among the three cytokines tested, compared with those for the SCD and NHC groups. Patients with VOC also differed from stable SCD patients and NHC by having notably lower IL-10 levels, as well as the lowest ratio of CD4(+) to CD8(+) T cells (0.7). The patterns of the proinflammatory cytokine IL-2 did not differ between VOC and stable SCD patients, but NHC had significantly lower IL-2 levels than both the VOC and SCD groups. Our results demonstrate coexisting levels, both high and low, of TH1- and TH2-type cytokines, as well as diminished levels of T-cell subsets in VOC. These results are discussed in an effort to better understand the importance of the immune system profile in the pathogenesis of sickle cell VOC. Since the possibility that a cytokine imbalance is implicated in the pathogenesis of sickle cell crisis has been raised, our results should prompt further investigation of the host immune response in terms of TH1 and TH2 balance in sickle cell crisis.

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Figures

FIG. 1.
FIG. 1.
Serum IL-2 levels in patients in vaso-occlusive crisis (VOC) (n = 26), stable SCD patients (n = 20), and normal healthy controls (NHC) (n = 18) were assessed by ANOVA and posthoc tests. Bars represent means and standard deviations. Greek letters indicate statistically significant (P < 0.05) differences between either VOC patients (α) or stable SCD patients (β) and NHC.
FIG. 2.
FIG. 2.
Distribution of serum IL-4 and IL-10 levels in patients in VOC, steady-state SCD patients, and normal healthy controls. (a) Serum IL-4 concentrations in patients in VOC (n = 26), steady-state SCD patients (n = 20), and NHC (n = 18) were assessed by ANOVA and posthoc tests. α, significant differences (P < 0.05) for VOC patients versus steady-state SCD patients and normal healthy controls. (b) Serum IL-10 concentrations in VOC patients, SCD patients, and NHC. Greek letters indicate significant differences (P < 0.05) between either VOC patients (α) or steady-state SCD patients (β) and NHC. Bars represent means and standard deviations.

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