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

Abstract

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.

Expression of interleukin-1 alpha, tumor necrosis factor alpha and interleukin-6 genes in astrocytes under ischemic injury

“…In neuron, TNFa can modulate calcium channels (Soliven and Albert, 1992), decrease catecholamine secretion (Soliven and Albert, 1992), alter synaptic transmission (Tancredi et al, 1992) and protect CNS neurons against metabolic-excitotoxic insults and promote calcium homeostasis (Cheng et al, 1994). IL-6 can induce astrocyte to secrete nerve growth factor (Frei et al, 1989). The ®ndings from this study as well as the many functions of IL-1, TNFa and IL-6 sustain the essential role of astrocytes in the immunologic response in brain under ischemia.…”

“…Relton and Rothwell (1992) have shown that the IL-1 receptor antagonist can reduce neuronal death induced by ischemia or excitotoxin. IL-1a is believed to be one of the key factors in triggering brain immune responses by inducing the expressions of IL-6 , Frei et al, 1989 and TNFa (Bethea et al, 1992;Chung and Benveniste, 1990). In neuron, TNFa can modulate calcium channels (Soliven and Albert, 1992), decrease catecholamine secretion (Soliven and Albert, 1992), alter synaptic transmission (Tancredi et al, 1992) and protect CNS neurons against metabolic-excitotoxic insults and promote calcium homeostasis (Cheng et al, 1994).…”

Lack of value of routine analysis of cerebrospinal fluid for prediction and diagnosis of external drainage–related bacterial meningitis

“…10,12 Lopez-Cortes and colleagues 11 found that CSF levels of tumor necrosis factor-␣, IL-1␤, IL-6, and IL-8 were significantly higher in neurosurgical patients with bacterial meningitis than in patients with asymptomatic aseptic meningitis. These inflammatory cytokines are synthesized intrathecally by activated leukocytes 7,24 and were found to be more specific predictors of bacterial meningitis, compared with cell counts, in the study by Lopez-Cortes and colleagues. We analyzed the predictive and diagnostic value of IL-6 in neurosurgical patients with external drains.…”

Temporal Profile of Cerebrospinal Fluid, Plasma, and Brain Interleukin-6 After Normothermic Fluid-Percussion Brain Injury: Effect of Secondary Hypoxia

“…Thus, IL-6 may be a marker for injury severity and/or secondary insults under these experimental conditions, but due to the nonsignificant elevations, these results warrant further investigation. IL-6 may be produced by several different cell types after TBI or other types of acute injury (Frei et al, 1989;Woodroofe et al, 1991;Taupin et al, 1993;Clark et al, 1996;Hans et al, 1999;Reyes et al, 1999;Morganti-Kossmann et al, 2007;Suzuki et al, 2009;Lu et al, 2009;Yan et al, 2012). The evidence for local synthesis of IL-6 and other cytokines by resident cells, including neurons, glia, and endothelial cells, has been reported (Ott et al, 1994;Shohami et al, 1994;MorgantiKossmann et al, 1997;Feuerstein et al, 1998;Ghirnikar et al, 1998;Wang et al, 2001).…”