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

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 (TNFalpha) 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 TNFalpha-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.

Role for glutathione in the hyposensitivity of LPS-pretreated mice to LPS anorexia.

To study the role of the redox state regulator glutathione (GSH) in bacterial lipopolysaccharide (LPS)-induced anorexia we measured total reduced GSH (trGSH) in liver, serum and brain in response to intraperitoneal (ip) lipopolysaccharide (LPS, 4 microg/mouse) injection in LPS-naïve and LPS-pretreated (4 microg/mouse given 3 days earlier) mice. LPS reduced food intake in LPS-naïve mice and LPS pretreatment attenuated this effect. LPS decreased trGSH at 24 hours after injection in LPS-naïve mice but 4 days later trGSH levels were upregulated in brain and liver, and this was associated with a significant attenuation of LPS-induced anorexia.