title: Eicosapentaenoic acid modulates CyA-induced proinflammatory cytokine over-expression in osteoblastic cells in vitro.
abstract: Several adverse outcomes are reported in subjects undergoing long term Cyclosporin A (CyA) treatment. Severe osteopenia has been described in clinical and experimental reports, while beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on bone metabolism are recognized. In the present study we investigated the effects of n-3 versus n-6 PUFAs on osteoblastic cells treated with CyA, evaluating the expression of interleukin (IL)-1&#223;, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in two different experimental protocols and the production of IL-6, IL-1&#223;, and tumor necrosis factor alpha (TNFalpha) in cells challenged simultaneously with CyA and eicosapentaenoic acid (EPA) for 48h. IL-1&#223; and IL-6 up-regulation, induced by CyA, was counteracted by the addition of EPA in both protocols; on the contrary, arachidonic acid (AA) magnified CyA the effects. COX-2 and iNOS levels were not modified by CyA treatment. These in vitro results, that substantiate clinical reports of CyA-induced osteopenia, demonstrate a beneficial effect of EPA on CyA-altered cytokine profile, opening new perspectives in the non-pharmacological management of adverse outcomes in CyA-treated patients.
authors.affiliation: Department of Medicine, University of Padova, Italy. estella.musacchio@unipd.it
authors.forename: E
authors.initials: E
authors.lastname: Musacchio
authors.forename: G
authors.initials: G
authors.lastname: Priante
authors.forename: C
authors.initials: C
authors.lastname: Valvason
authors.forename: B
authors.initials: B
authors.lastname: Baggio
authors.forename: L
authors.initials: L
authors.lastname: Sartori
mesh_terms: D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016572:Cyclosporine; D015118:Eicosapentaenoic Acid