Pattern of Serum Cytokine Expression and T-Cell Subsets in Sickle Cell Disease Patients in Vaso-Occlusive Crisis

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.

Blood Viscosity and the Expression of Inflammatory and Adhesion Markers in Homozygous Sickle Cell Disease Subjects with Chronic Leg Ulcers

“…This marked an important finding since activation of the endothelium was brought about by red cells alone, not components of the plasma. Sickle cell disease subjects have been shown to be unusually susceptible to a variety of infections possibly as a consequence of reticuloendothelial dysfunction [33,37–40]. In light of such observations and the comparability of IL-10 concentration between SS n and SS u in the present study, it seems possible that there may be an imbalance between the expression of inflammatory and anti-inflammatory immune responses in sickle cell disease subjects with chronic leg ulcers.…”

Immunological Characterization in Malaria Patients with and without the Sickle-Cell Trait

“…These cytokines are also involved in the pathogenesis of the malaria caused by the infection, leading to the appearance of symptoms of varying severity. The asymptomatic sicklers had significantly lower expression of tumor necrosis factor than the non-sicklers with severe malaria, but these two groups showed similar expression of interferon-gamma, interleukin-4 and interleukin-6, IL12, IL18 [34]. Immunity takes over with CD4 + T-cells becoming the main producers of interleukin-12 defines type 1 helper cells and is associated with a strong cell-mediated immunity with production of IL-4, 5, 6, 9 and 10.…”

Preconditioning with Hemin Decreases Plasmodium chabaudi adami Parasitemia and Inhibits Erythropoiesis in BALB/c Mice

“…Malaria and other hemolytic disorders are characterized by enhanced susceptibility to bacterial and viral infections, and increased levels of IL-4, IL-6 and IL-10 [1], [2], [3]. These reports suggest a T helper (T h ) 2 bias in chronic and acute hemolytic conditions that may contribute to altered cellular immunity.…”