Overexpression of interleukin-6 in the central nervous system of transgenic mice increases central but not systemic proinflammatory cytokine production

Elena Di Santo, Tonino Alonzi, Elena Fattori, Valeria Poli, Gennaro Ciliberto, Marina Sironi, Paola Gnocchi, Paola Ricciardi-Castagnoli, Pietro Ghezzi

Research output: Contribution to journalArticlepeer-review

Abstract

Production of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6), in the brain is increased in various diseases. To investigate the relationships between the effect of overproduction of IL-6 in the brain on central and peripheral production of TNF, IL-1β and IL-6 itself, we used transgenic mice (NSE-hIL-6) where neuronal human IL-6 expression under the control of the neuronal specific enolase promoter results in astrocytosis and gliosis. These mice had higher cerebral endogenous IL-6 (12-fold), IL-1β (12-fold) and TNF (4-fold) production measured in brain homogenates after intracerebroventricular (i.c.v.) injection of 2.5 μg LPS, lipopolysaccharide (LPS) than wild-type mice (no TNF or IL-1 were detectable in saline-injected NSE or control mice). Cerebral cytokines production was also increased in NSE-hIL-6 mice treated i.p. with LPS doses that do not normally induce cytokines in the brain. The induction of peripheral (serum or spleen) TNF, IL-1β or IL-6 was the same in all these experiments in NSE-hIL-6 and wild-type mice. Furthermore, using microglial cell clone pretreated in vitro with IL-6, we noted an increase in LPS-induced TNF and IL-6 production and proliferation of pretreated cells than control. This study indicates that overproduction of IL-6 in the central nervous system (CNS) may ultimately result in increased central production of inflammatory cytokines, probably due to increased proliferation and activation of the cells which produce cytokine in the CNS.

Original languageEnglish
Pages (from-to)239-244
Number of pages6
JournalBrain Research
Volume740
Issue number1-2
DOIs
Publication statusPublished - Nov 18 1996

Keywords

  • interleukin-1
  • interleukin-6
  • lipopolysaccharide
  • transgenic mice
  • tumor necrosis factor

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Overexpression of interleukin-6 in the central nervous system of transgenic mice increases central but not systemic proinflammatory cytokine production'. Together they form a unique fingerprint.

Cite this