Altered levels of pro-inflammatory cytokines in sickle cell disease patients during vaso-occlusive crises and the steady state condition

Abstract

Objective: This study aimed to evaluate serum levels of pro-inflammatory cytokines and TGF-␤ in sickle cell disease (SCD) patients, and to compare the results during vaso-occlusive crisis (VOC) or steady state (StSt) conditions. Methods: 54 SCD patients (37HbSS and 17S␤ + Thal) were enrolled in the study and evaluated in two groups as follows; group A consisted of 39 VOC patients and group B comprised 15 StSt patients. Nineteen healthy volunteers were included as controls. Circulating levels of IL-1, IL-6, IL-8, IL-17,TNF-␣ and TGF-␤ were measured using ELISA. Results: Patients in VOC showed higher mean levels of all cytokines than those found in steady-state patients, but this was only marginally significant for IL-8 levels (P = 0.08). Increased levels of TGF-␤ and IL-17 were found in StSt patients versus normal controls (P = 0.004 and P<0.0001 respectively). A positive correlation was observed between IL-8 and IL-17 in both groups of patients (P = 0.002 and P = 0.005 respectively). Decreased levels of TNF-␣, IL-1␤ and IL-17 were found in hydroxyurea-treated patients. Additionally, significantly higher levels of IL-6 and IL-8 were observed in hydroxyurea-treated and untreated patients than in controls respectively (P = 0.04 and P = 0.01). Conclusions: Our findings indicate that pro-inflammatory cytokines, especially IL-8 and IL-17, could be used as related markers for assessing disease severity, and consequently therapeutic intervention.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

“…Interestingly, many inflammatory cytokines that are involved in neurogenic inflammation are significantly increased in patients with SCD compared to controls, and increase further during acute vaso-occlusive crisis. (Francis & Haywood 1992; Keikhaei et al , 2013; Pathare et al , 2004; Sarray et al , 2015) Our data support the need for further study into the downstream effects of chronic SP elevation in baseline health and further SP elevation during acute pain. In addition, risk factors and reasons for increased SP levels in patients with SCD require further investigation.…”

A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria

“…Vaso-occlusion crisis is a hallmark of SCD but the mechanism(s) responsible for triggering VOC in SCD is likely a result of complex interplay of precipitating factors at multiple stages. However, it has been shown that SCD subjects in VOC have higher levels of pro-inflammatory cytokines compared with those in steady state [53]. Since malaria has been shown to be a precipitating factor for VOC in SCD patients [6], it is plausible that, the chronic inflammatory status in the SCD malaria-positive patients could influence parasite clearance directly, or indirectly, through yet- undetermined action of anti-malarial drugs in SCD patients.…”

Sickle cell disease: a natural model of acute and chronic pain

“…The severe pathophysiology triggered by sickled RBCs includes: 1) blood vessel obstruction resulting in tissue ischemia (vaso-occlusion)[13]; 2) reperfusion injury after vaso-occlusion [13]; 3) shortened RBC survival resulting in severe chronic hemolytic anemia and release of free heme[55] and other RBC intracellular contents[26; 52]; and 4) chronic inflammation. [28; 30] SCD is a multi-organ system disease due to the chronic and ongoing effects of repeated vaso-occlusion and subsequent ischemia-reperfusion injury. [53] [74]…”

“…COX-2, IL-6 and TLR4 receptors[28] and second messengers PKC and CaMKII activation are increased in the spinal dorsal horn [71], and inhibition of PKCδ attenuates the SCD pain behavior[22]…”