In vitro cytotoxicity of human endothelial cells in polymyalgia rheumatica and giant cell arteritis.
We studied sera from 20 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA), 15 patients with systemic lupus erythematosus (SLE), 15 patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangietasia) and 33 age and sex matched controls for cytotoxicity against human endothelial cells using a 51Cr release assay. We observed increased levels of endothelial cytotoxic activity in the PMR/GCA sera compared with controls (P less than 0.001). This cytotoxicity was predominantly found in the GCA group, where 7 out of 10 patients (70%) demonstrated significant cytotoxicity. Sequential studies showed that the cytotoxic activity returned to normal when the disease was under control. Although 7 SLE and 3 CREST sera had significant cytotoxic activity, as a group they did not differ from controls (P less than 0.05). Pre-incubation with soybean trypsin inhibitor suppressed the cytotoxic activity in the positive sera suggesting the cytotoxicity is mediated via a protease mechanism. Our results demonstrate the presence of a cytotoxic factor in the serum of patients with PMR/GCA which may play an important role in the pathogenesis of the vascular lesions observed in these disorders.