CYCLOSPORINE-A BLOCKS INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN B-LYMPHOCYTES

The effects of cyclosporin A (CSP) on tumor necrosis factor-alpha (TNF-alpha) RNA levels and protein production in human B cells and a B cell line were studied. The ability of CSP to block induction of RNA was compared to its inhibition of protein production in response to anti-igM, phorbol ester (PMA) and platelet-activating factor (PAF). PAF is a phospholipid which has recently been found to activate human B cells. CSP blocks PAF-induced TNF-alpha RNA-from the Ramos cell line, as well as inhibiting the enhancement of TNF protein production from both freshly isolated and Ramos B cells. CSP also blocks anti-lg induced TNF-alpha RNA and protein but does not inhibit PMA-induced TNF-alpha. We conclude that B cells, like T cells, have CSP-independent and CSP-dependent signaling pathways and that PAF signaling is dependent upon a CSP-sensitive factor. (C) 1994 Academic Press, Inc.