TNF and endothelial dysfunction: Whilst small open label studies of tumor necrosis factor (TNF) inhibition have suggested benefit (26) in disease control and improvement in abnormal endothelial dysfunction, a large randomized placebo controlled trial of etanercept, a TNF receptor protein, has shown no benefit in patients with GPA; in fact these patients had an increased risk of malignancy, which may in part have related to the inclusion of patients previously exposed to large doses of cyclophosphamide (27).