On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases.
Interleukin 6 (IL6) 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 IL6 was detected in the CNS. IL6 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 IL6 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 IL6. In astrocytes, the infection resulted in the induction of the 1.3-kb messenger RNA IL6. Besides its effect on the development of B cell immunity in the brain, IL6 may be involved in repair mechanisms initiated in the course of viral-induced tissue damage. As shown here, IL6 induced an increase of the secretion of a neurotrophic factor, nerve growth factor by astrocytes. Thus, the intrathecal synthesis of IL6 may be part of the host response to infection favoring immune-mediated elimination of the infectious agent as well as trophic support for neurons.
Frei
K
K
Department of Neurosurgery, University Hospital, Zürich, Switzerland.
Malipiero
U V
UV
Leist
T P
TP
Zinkernagel
R M
RM
Schwab
M E
ME
Fontana
A
A
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D015850:Interleukin-6; D007378:Interleukins / Q000134:cerebrospinal fluid / Q000502:physiology*; D008216:Lymphocytic Choriomeningitis / Q000503:physiopathology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009457:Neuroglia / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus
D015850:Interleukin-6; D007378:Interleukins; D009414:Nerve Growth Factors