Plasma Levels of Tumor Necrosis Factor and Endothelial Response in Patients with Chronic Arterial Obstructive Disease or Raynaud's Phenomenon

Abstract

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudi cation and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t- PA), and its inhibitor (PAI) were also determined as markers of release from the endothe lium, while the fragment 1+2 of prothrombin (F1+2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects. There were strong direct correlations between TNF and age ( r=0.57, P=0.0001); TNF and t-PA (r=0.43, P=0.002); and TNF and vWF (r=0.52, P=0.0001). The association of TNF with vWF was indepen dent of other variables. The present study suggests that TNF plays an important role in the pathophysiology of arterial diseases of atherosclerotic origin, especially during aging.