Cytokine profile of sickle cell disease in Oman

Abstract

The aim of our study was to assess the cytokine profile of sickle cell disease (SCD) patients in steady state and in vaso-occlusive crisis (VOC). VOC has a complex nature, involving interactions between sickle red blood cells (RBC), the endothelium, and leucocytes. Endothelial damage due to recurrent adhesion of sickle RBCs may disrupt endothelial function, leading to altered cytokine release. It is therefore pertinent to study the cytokine profile of SCD patients in steady state and in crisis prior to exploring its contribution to vasoocclusive manifestations, since it is believed that an altered balance of proinflammatory and anti-inflammatory cytokines plays an important role in painful crisis. Cytokines including IL1b, IL-2, IL-4, IL-6, IL-8, TNF-a, and IFN-g were measured by commercially available ELISA kits in SCD patients (n = 60); in steady state (n = 26) and in painful crisis (n = 34) and compared with nonanemic age-and sex-matched normal Omani controls (n = 20). SCD patients in crisis showed elevated levels of TNF-a (P < 0.092) and IL-6 (P < 0.024) when compared with steady state. It was also observed that SCD patients in steady state showed a significant elevation in IL-1b (P < 0.04), IL-6 (P < 0.0001), and IFN-g (P < 0.02) as compared to normal subjects. It is thus evident that both type I and type II cytokines are significantly altered in SCD patients. In steady state, type II proinflammatory cytokines are elevated, whereas in crisis, an additional augmentation of type I cytokines occurs, with persistent elevation of type II cytokines, emphasizing the role of perturbed endothelium and activated monocytes in the pathophysiology of vaso-occlusion in sickle cell crisis. Am.

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

“…The same group (Bao et al, 2013) also presented data suggesting that regulatory B cells (Bregs) from alloimmunized and non-alloimmunized SCD patients differ in their ability to produce IL10 upon stimulation and dampen monocyte activation despite comparable frequencies of Bregs (CD19 + CD24 hi CD38 hi and CD24 hi CD27 + subsets) supporting an altered immunoregulatory state in alloimmunized SCD patients. Investigations of cytokine levels during acute SCD-related complications have shown increased neutrophil chemotaxis, monocyte phagocytosis and levels of IL6 and TNF during VOC (Graido-Gonzalez et al, 1998;Pathare et al, 2004). Additionally, circulating and bronchoalveolar lavage fluid levels of IL8 are elevated in SCD patients with ACS compared to SCD patients at steady state and non-SCD patients (Abboud et al, 2000).…”

Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy

“…Others, however, have found a small but significant elevation in circulating IFN-␥ levels in steady-state SCD individuals [16]. In contrast to the lack of alteration in circulating IFN-␥ in our population of steady-state patients, we found IFN-␥ mRNA expression to be increased significantly in the neutrophils of these individuals compared with control individuals; previous studies have also demonstrated that SCD lymphocytes, when cultured in the presence of activating phytohemagglutinin, produce significantly higher levels of IFN-␥ than control lym- phocytes [28].…”

Microvascular oxygen consumption during sickle cell pain crisis

“…Our findings of elevated inflammatory biomarkers during sickle cell pain crisis are consistent with previous studies showing elevated neutrophil count and CRP in steady state with further elevation during pain crisis, though we did not observe an elevated neutrophil count in steady state compared with healthy individuals as previously reported. 13,14 The observational nature of this study does not allow us to causally link inflammation with increased oxygen consumption; however, these data emphasize the relevance of inflammation to the pathophysiology of sickle cell disease, especially during pain crisis. …”