Modulation of endothelial cell activation in sickle cell disease: a pilot study

The vessel wall endothelium undoubtedly plays a role in the vascular pathob iology of sickle cell disease. This pilot study tested the feasibility of u sing an inhibitor of nuclear factor (NF)-kappaB, a transcription factor, to modify the endothelial activation state of patients with this vascular dis ease, For a total of 7 separate drug exposure tests, 3 subjects with sickle cell disease took sulfasalazine (given orally at 1 g every 8 hours), and t he activation state of their circulating endothelial cells (CECs) was asses sed using immunofluorescence microscopy, Companion studies were also perfor med using sulfasalazine in sickle transgenic mice to verify its effect simu ltaneously on both CECs and vessel wall endothelium, Both CECs and tissue v essel wall endothelium in sickle mice have an activated phenotype, In these mice sulfasalazine significantly reduced CEC expression of vascular cell a dhesion molecule (VCAM), intracellular adhesion molecule (ICAM), and E-sele ctin, and it correspondingly reduced expression of these molecules in some tissue vessels, In humans with sickle cell disease, sulfasalazine significa ntly reduced CEC expression of VCAM, ICAM, and E-selectin, but it did not r educe expression of tissue factor, Addition of a second transcription facto r inhibitor, salsalate, did not change this result, This pilot study sugges ts that endothelial cell activation state can be modified and down-regulate d in vivo by sulfasalazine.(Blood. 2001;97:1937-1941) (C) 2001 by The Ameri can Society of Hematology.