On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases

Abstract

Interleukin 6 (IL 6) was found to be produced in the central nervous system (CNS) of ICR +/+ mice infected with lymphocytic choriomeningitis virus (LCMV) or with vesicular stomatitis virus (VSV). When infecting athymic ICR nu/nu mice which cannot develop T cell-mediated meningitis after LCMV infection, no significant synthesis of IL 6 was detected in the CNS. IL 6 was found, however, to be produced intrathecally in ICR nu/nu mice infected with VSV, which causes a T cell-independent acute encephalitis. This suggested that IL 6 may also originate from cells not belonging to the T cell compartment. Indeed, in vitro assays showed that both virus-infected microglial cells and astrocytes secreted IL 6. In astrocytes, the infection resulted in the induction of the 1.3-kb messenger RNA IL 6. Besides its effect on the development of B cell immunity in the brain, IL 6 may be involved in repair mechanisms initiated in the course of viral-induced tissue damage. As shown here, IL 6 induced an increase of the secretion of a neurotrophic factor, nerve growth factor by astrocytes. Thus, the intrathecal synthesis of IL 6 may be part of the host response to infection favoring immune-mediated elimination of the infectious agent as well as trophic support for neurons.