An inhibitor of the toxicity of tumour necrosis factor in the serum of patients with sarcoidosis, tuberculosis and Crohn's disease.
The activated macrophages present in the T cell-dependent granulomata of sarcoidosis and tuberculosis are primed for enhanced release of cytokines including tumour necrosis factor (TNF or cachectin). Release of this cytokine can induce an acute-phase response, fever, and necrosis in suitably prepared sites of inflammation; if chronic, its presence may contribute to weight loss. These clinical features are characteristic of tuberculosis, but not of sarcoidosis, though alveolar macrophages from both diseases release large quantities of TNF in vitro. We therefore postulated the presence in sarcoidosis patients of an inhibitor of TNF. We have studied levels of TNF inhibitory activity by determining the quantity of TNF required to give 50% kill of L929 cells in the presence of 20% heat-inactivated serum derived from various disease states (37 sarcoidosis, 13 tuberculosis, 13 Crohn's disease, 17 healthy donors). Normal sera used in this way do not inhibit significantly, but inhibition of TNF toxicity is caused by most sera from both sarcoidosis and tuberculosis. Used at 20%, five out of 37 sarcoidosis sera and one out of 13 tuberculosis sera caused complete inhibition of TNF, even when the latter was added at 100 times the concentration required to give 50% kill in control wells. This inhibitor may have an important physiological role.
Department of Medicine, University College & Middlesex School of Medicine, London, England.
N
N
Foley
C
C
Lambert
M
M
McNicol
N
N
Johnson
G A
GA
Rook
D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D002470:Cell Survival; D003424:Crohn Disease / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000097:blood*; D014397:Tuberculosis, Pulmonary / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000209:Acute-Phase Proteins; D014409:Tumor Necrosis Factor-alpha