Effects of ifn-b on TRAIL and decoy receptor expression in different immune cell populations from MS patients with distinct disease subtypes

Using quantitative RT-PCR, we compared mRNA levels for TRAIL [tumor necrosis factor (TNF)related apoptosis-inducing ligand] and its receptors in various immune cell subsets derived from the peripheral blood of untreated normal subjects (NS) and patients with distinct subtypes of multiple sclerosis (MS): active relapsing-remitting MS (RRA), quiescent relapsing-remitting MS (RRQ), secondary-progressive MS (SPMS) or primary-progressive MS (PPMS). Consistent with a role for TRAIL in the mechanism of action of interferon- (IFN- ß), TRAIL mRNA levels were increased in monocytes from patients clinically responsive to IFN-ß (RRQ) but not those unresponsive to this therapeutic (RRA). TRAIL-R3 (decoy receptor) expression was elevated in T cells from untreated RRMS patients while IFN-ß therapy reversed this increase suggesting that IFN-ß may promote the apoptotic elimination of autoreactive T cells by increasing the amount of TRAIL available to activate TRAIL death receptors. Serum concentrations of soluble TRAIL were increased to a similar extent by IFN-ß therapy in RRQ, RRA and SPMS patients that had not generated neutralizing antibodies against this cytokine. Although our findings suggest altered TRAIL signaling may play a role in MS pathogenesis and IFN-ß therapy, they do not support use of TRAIL as a surrogate marker for clinical responsiveness to this therapeutic.