Open Access

ARTICLE

Role for nerve growth factor in the in vivo regulation of glutathione in response to LPS in mice

Denis Arsenijevic¹, Noemi Hernadfalvi¹, Claudia von Meyenburg¹, Brigitte Onteniente², Denis Richard³, Wolfgang Langhans¹

1 Institute of Animal Sciences, ETH Zurich, Schwerzenbach, Switzerland
2 ISERM UMR421, Creteil, France
3 Department of Anatomy and Physiology, Laval University, Quebec, Canada

* Corresponding Author: Denis Arsenijevic,

European Cytokine Network 2007, 18(2), 93-101. https://doi.org/10.1684/ecn.2007.0091

Accepted 04 June 2007;

Abstract

Since the redox state regulator glutathione (GSH), which influences lipopolysaccharide (LPS) anorexia, may be controlled by cytokines, we studied the roles of tumour necrosis factor-alpha (TNFα) and nerve growth factor (NGF) in the GSH response to intraperitoneal (ip) LPS injection in mice. Basal NGF and total reduced GSH (trGSH) levels were up-regulated in brain and liver of TNFα-knock-out (KO) mice, and this was associated with attenuated LPS anorexia. The increases in NGF and trGSH presumably contributed to the attenuated anorexia in response to LPS because transgenic mice over-expressing NGF (NGF-tg mice) also had increased trGSH levels and displayed attenuated anorexia compared to the corresponding wild type (WT) mice. Attenuated LPS anorexia in NGF-tg mice was accompanied by reduced serum TNFα and IFNγ levels compared to WT mice. In response to a second injection of LPS, NGF and trGSH levels, but not TNFα levels changed. This suggests that in vivo tissue trGSH changes following LPS in LPS-naïve or LPS-pretreated mice are regulated by NGF rather than TNFα. The finding that genetic TNFα deficiency did not inhibit the acute trGSH response to LPS supports this interpretation. In sum, the results indicate i) that a decrease or increase in NGF is accompanied by a decrease or increase in trGSH levels and ii) that elevated NGF and/or trGSH levels attenuate some of the responses to LPS such as anorexia and cytokine production.

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