title: Anti-inflammatory effects of inosine in human monocytes, neutrophils and epithelial cells in vitro.
abstract: Inosine is an endogenous purine, which has been recently shown to exert immunomodulatory, anti-inflammatory and anti-shock effects in rodent experimental systems. Some of these actions may be related to partial adenosine receptor agonistic effects. It has not been investigated previously whether inosine exerts similar immunomodulatory or anti-inflammatory effects in human cells or enzymes. Here we investigated the effects of inosine on the activation of human monocytes, neutrophils and epithelial cells in vitro. Furthermore, using a human inosine-5'-monophosphate dehydrogenase (IMPDH) enzyme, we examined the potential effects of inosine on the activity of IMPDH, an enzyme involved in the regulation of certain inflammatory/immune processes. Tumor necrosis factor alpha (TNF-alpha) production of bacterial lipopolysaccharide (LPS) stimulated whole blood was used as an indicator of human monocyte activation. The response was dose-dependently, partially suppressed in the presence of inosine. Inosine exerted a dose-dependent and, at the highest dose (3 mM), complete inhibition of the ability of human neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) to induce cytochrome C reduction in vitro. In the human colon cancer cell line HT-29, inosine dose-dependently attenuated the production of IL-8. Inosine failed to affect the activity of IMPDH. Taken together, we conclude that inosine exerts anti-inflammatory effects in many human cell types. Further studies need to establish whether inosine supplementation exerts anti-inflammatory effects in human beings.
authors.affiliation: Inotek Corporation, Beverly, MA 01915, USA.
authors.forename: A
authors.initials: A
authors.lastname: Marton
authors.forename: P
authors.initials: P
authors.lastname: Pacher
authors.forename: K G
authors.initials: KG
authors.lastname: Murthy
authors.forename: Z H
authors.initials: ZH
authors.lastname: Németh
authors.forename: G
authors.initials: G
authors.lastname: Haskó
authors.forename: C
authors.initials: C
authors.lastname: Szabó
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D003574:Cytochrome c Group / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007168:IMP Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D007288:Inosine / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D003574:Cytochrome c Group; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007288:Inosine; D007168:IMP Dehydrogenase