In vitro modulation of the multiple sclerosis (MS)-associated retrovirus by cytokines: implications for MS pathogenesis.

Abstract

Multiple sclerosis (MS)-associated retrovirus (MSRV) is a component of the human endogenous retrovirus (HERV)-W family, with gliotoxic and superantigenic properties, related to MS clinical progression, and transactivated by viral agents. The authors studied MSRV modulation by cytokines involved in vivo in MS course, utilizing peripheral blood mononuclear cells from MSRV-positive and MRSV-negative individuals. Cultured cells from MSRV-negative subjects did not produce virus, whereas spontaneous MSRV release was detected in cultures from MSRV-positive donors; virus release was increased by interleukin (IL)-4 and IL-6 and, to a greater extent, by the detrimental cytokines interferon gamma and tumor necrosis factor (TNF)alpha. Interferon beta, used in MS therapy, inhibits MSRV release. A parallel between the effects of these cytokines on MSRV production in vitro and on MS disease in vivo is observed, which deserves further elucidations.