title: Atorvastatin inhibits the inflammatory response caused by anti-M(3) peptide IgG in patients with primary Sjögren's syndrome.
abstract: Experimental and clinical investigations have revealed that statins can down-regulate acute and chronic inflammatory processes. Whether statins express anti-inflammatory activities in the salivary glands in patients with primary Sjögren's syndrome (pSS) is not known. The in vitro and in vivo effect of atorvastatin on rat submandibular gland treated with anti-M(3) peptide IgG purified from SS patients was studied. The anti-inflammatory effects of atorvastatin were assessed by measuring the levels of IL-1β, PGE(2) and MMP-3 by ELISA. Atorvastatin inhibited the increase in the production of IL-1β, PGE(2) and MMP-3 in submandibular glands treated with anti-M(3) peptide IgG. A positive correlation between IL-1β production with accumulation of PGE(2) and MMP-3 was observed. Rats pre-treated orally with atorvastatin (30 mg kg(-1)) or vehicle (phosphate-buffered solution) once a day for three consecutive days impaired the increment in the production of IL-1β, PGE(2) and MMP-3 in the submandibular gland in the presence of anti-M(3) peptide IgG. In conclusion, the anti-inflammatory effects of atorvastatin are dependent upon inhibition of production of a pro-inflammatory cytokine (IL-1β) and pro-inflammatory mediators such as PGE(2) and MMP-3. These data suggest that atorvastatin may constitute an anti-inflammatory effect in SS.
authors.affiliation: Pharmacology Unit, School of Dentistry, Buenos Aires University, Marcelo T de Alvear 2142-4 "B"-1122AAH Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Reina
authors.forename: Daniela
authors.initials: D
authors.lastname: Passafaro
authors.forename: Leonor
authors.initials: L
authors.lastname: Sterin-Borda
authors.forename: Enri
authors.initials: E
authors.lastname: Borda
mesh_terms: D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000069059:Atorvastatin; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors* / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*; D013363:Submandibular Gland / Q000187:drug effects* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001323:Autoantibodies; D006538:Heptanoic Acids; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D010446:Peptide Fragments; D011758:Pyrroles; D043587:Receptor, Muscarinic M3; D000069059:Atorvastatin; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone