Pathare Anil, Al Kindi Salam, Alnaqdy Adel Alwan, Daar Shahina, Knox-Macaulay Huxley, Dennison David
Department of Haematology, Sultan Qaboos University Hospital, Sultanate of Oman.
Am J Hematol. 2004 Dec;77(4):323-8. doi: 10.1002/ajh.20196.
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 vaso-occlusive manifestations, since it is believed that an altered balance of proinflammatory and anti-inflammatory cytokines plays an important role in painful crisis. Cytokines including IL-1beta, IL-2, IL-4, IL-6, IL-8, TNF-alpha, and IFN-gamma 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-alpha (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-1beta (P < 0.04), IL-6 (P < 0.0001), and IFN-gamma (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.
我们研究的目的是评估镰状细胞病(SCD)患者在病情稳定期和血管闭塞性危机(VOC)期间的细胞因子谱。VOC具有复杂的性质,涉及镰状红细胞(RBC)、内皮细胞和白细胞之间的相互作用。镰状RBC反复黏附导致的内皮损伤可能会破坏内皮功能,从而导致细胞因子释放改变。因此,在探讨其对血管闭塞性表现的影响之前,研究SCD患者在病情稳定期和危机期的细胞因子谱是很有必要的,因为据信促炎细胞因子和抗炎细胞因子平衡的改变在疼痛危机中起重要作用。通过市售的ELISA试剂盒测定了SCD患者(n = 60)的细胞因子,包括IL-1β、IL-2、IL-4、IL-6、IL-8、TNF-α和IFN-γ;其中病情稳定期(n = 26)和疼痛危机期(n = 34),并与年龄和性别匹配的非贫血正常阿曼对照组(n = 20)进行比较。与病情稳定期相比,处于危机期的SCD患者TNF-α(P < 0.092)和IL-6(P < 0.024)水平升高。还观察到,与正常受试者相比,病情稳定期的SCD患者IL-1β(P < 0.04)、IL-6(P < 0.0001)和IFN-γ(P < 0.02)显著升高。因此很明显,I型和II型细胞因子在SCD患者中均有显著改变。在病情稳定期,II型促炎细胞因子升高,而在危机期,I型细胞因子进一步增加,II型细胞因子持续升高,这强调了内皮紊乱和活化单核细胞在镰状细胞危机血管闭塞病理生理学中的作用。