LIPOPOLYSACCHARIDE (LPS)-INDUCED AND MURAMYL DIPEPTIDE (MDP)-INDUCED ANOREXIA DURING REFEEDING FOLLOWING ACUTE FASTING - CHARACTERIZATION OF BRAIN CYTOKINE AND NEUROPEPTIDE SYSTEMS MESSENGER-RNA

We investigated the effectiveness of lipopolysaccharide (LPS) and mura myl dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted Wistar rats allowed to refeed. We also assayed for chan ges in mRNA levels of IL-1 system components, TNF-alpha, TGF-beta 1, g lycoprotein 130 (gp 130), leptin receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NTPY), glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions. The data show that LPS and MDP induced anorexia differentially during refeeding. LPS-induced ano rexia was of a stronger magnitude and duration than that of MDP. RNase protection assays showed that LPS and MDP significantly increased the expression of IL-I beta, IL-1 receptor type I, and TNF-alpha mRNAs in the cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP treatment, on the other hand, induced a stronger incre ase in hypothalamic levels of IL-1 receptor antagonist (IL-1Ra) and TG F-beta 1 mRNAs relative to LPS. In addition, competitive RT-PCR analys is showed that LPS induced an eleven-fold increase in IL-1 alpha mRNA in the hypothalamus relative to vehicle. These findings suggest that L PS and MDP mediate anorexia through different cytokine mechanisms. A s tronger up-regulation of anti-inflammatory cytokines (IL-1Ra and TGF-b eta 1) mRNA expression by MDP may be involved in the weaker MDP-induce d anorexia relative to LPS. No significant changes were observed in th e peptide components examined except for an up-regulation in cerebella r gp 130 mRNA and down-regulation of hypothalamic GR mRNA expression i n response to LPS or MDP. This study shows that LPS and MDP induce ano rexia in fasted rats allowed to refeed, and suggests an important role for endogenous cytokine-cytokine interactions. (C) 1998 Elsevier Scie nce B.V. All rights reserved.