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.