Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis

Abstract

Tumor necrosis factor (TNF) is a monokine released by macrophages and is important in the inflammatory response. We compared the spontaneous release of TNF by alveolar macrophages (AMs) from patients with symptomatic pulmonary sarcoidosis, some of whom were receiving corticosteroid therapy, with AMs from control smokers. TNF was released from AMs of sarcoidosis patients at significantly higher levels than was released by control AM subjects (sarcoids, 15 U/ml [0 to 1140 U (median [range]]); controls, all less than 5 U/ml, p less than 0.01). By using a specific polyclonal antibody, the detected TNF was found to be TNF-alpha. Among the sarcoidosis patients, the amount of TNF released was significantly lower for those patients given treatment with corticosteroids (5 U/ml [0 to 15 U/ml]) compared with untreated persons (50 U/ml [0 to 1140 U/ml], p less than 0.05). In vitro studies demonstrated that incubation of peripheral blood monocytes or AMs with dexamethasone for 42 hours suppressed subsequent release of TNF. We conclude that AMs from sarcoidosis patients often spontaneously release TNF and this release is suppressed by prolonged corticosteroid therapy.