Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide

Gram-negative bacteria-derived lipopolysaccharide (LPS or endotoxin) is kno wn to play an important role in immune and neurological manifestations duri ng bacterial infections. LPS exerts its effects through cytokines, and peri pheral or brain administration of LPS activates cytokine production in the brain. in this study, we investigated cytokine and neuropeptide mRNA profil es in specific brain regions and peripheral organs, as well as serum tumor necrosis factor (TNF)-alpha protein levels, in response to the intraperiton eal administration of LPS. For the first time, the simultaneous analysis of interleukin (IL)-1 beta system components (ligand, signaling receptor, rec eptor accessory proteins, receptor antagonist), TNF-alpha, transforming gro wth factor (TGF)-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, and pro-opiomelanocortin (op ioid peptide precursor) mRNAs was done in samples from specific brain regio ns in response to peripherally administered LPS. The same brain region/orga n sample was assayed for all cytokine mRNA components. Peripherally adminis tered LPS up-regulated pro-inflammatory cytokine (IL-1 beta and/or TNF-alph a) mRNAs within the cerebral cortex, cerebellum, hippocampus, spleen, liver , and adipose tissue. LPS also increased plasma levels of TNF-ru protein. L PS did not up-regulate inhibitory (anti-inflammatory) cytokine (IL-1 recept or antagonist and TGF-beta \1) mRNAs in most brain regions (except for IL-1 receptor antagonist in the cerebral cortex and for TGF-beta1 in the hippoc ampus), while they were increased in the liver, and IL-1 receptor antagonis t was up-regulated in the spleen and adipose tissue. Overall, peripherally administered LPS modulated the levels of IL-1 beta system components within the brain and periphery, but did not affect the neuropeptide-related compo nents studied. The data suggest specificity of transcriptional changes indu ced by LPS and that cytokine component up-regulation in specific brain regi ons is relevant to the neurological and neuropsychiatric manifestations ass ociated with peripheral LPS challenge. (C) 2001 Elsevier Science Inc.