title: High-density lipoproteins inhibit urate crystal-induced inflammation in mice.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of action of high-density lipoproteins (HDL) in monosodium urate (MSU) crystal-induced inflammation -that is, gouty inflammation, in vivo.
  
  
  METHODS
  Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL)-1 receptor antagonist (IL-1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer and May-Grünwald-Giemsa staining. The cytokine production and expression in the pouch were measured by ELISA and quantitative RT-PCR.
  
  
  RESULTS
  MSU crystals induced leucocyte infiltration, mostly neutrophils, and the release of IL-1β, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 2 (CCL2) and IL-1Ra in pouch fluids. TNF remained under the detection limit. MSU crystals triggered IL-1β, IL-6 and CXCL1 expression in both pouch exudates and membranes, whereas CCL2 and TNF mRNA were not modulated. The co-injection of MSU crystals and HDL inhibited leucocyte influx by 59% and neutrophil infiltration by 83% and, in turn, both protein and mRNA levels of all assessed proinflammatory cytokines were reduced, but not those of IL-1Ra. Similar results were obtained when mice were injected with MSU crystals pretreated with HDL or TNF instead of crystals. When HDL and IL-1Ra were added together they displayed additional inhibition, suggesting different mechanisms of action.
  
  
  CONCLUSIONS
  This study demonstrated that HDL may represent an important factor in the modulation of gouty inflammation by acting on both tissue and infiltrating cells -that is, synovial tissue and synovial fluid cells. HDL display anti-inflammatory activity, in part, by interacting with crystals but also by directly acting on cells.
authors: Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors: Anna
authors: A
authors: Scanu
authors: Center of Experimental Surgery, University of Padova, Padova, Italy.
authors: Roberto
authors: R
authors: Luisetto
authors: Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors: Francesca
authors: F
authors: Oliviero
authors: Division of Immunology and Allergy, Hans Wilsdorf Laboratory, IARG, Department of Internal Medicine, University Hospital and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors: Lyssia
authors: L
authors: Gruaz
authors: Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors: Paolo
authors: P
authors: Sfriso
authors: Division of Immunology and Allergy, Hans Wilsdorf Laboratory, IARG, Department of Internal Medicine, University Hospital and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors: Danielle
authors: D
authors: Burger
authors: Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors: Leonardo
authors: L
authors: Punzi
mesh_terms: D000818:Animals; D001415:Back; D018932:Chemokine CCL2 / Q000187:drug effects / Q000276:immunology; D054360:Chemokine CXCL1 / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006073:Gout; D007249:Inflammation / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000187:drug effects / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000187:drug effects / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D051379:Mice; D040521:Subcutaneous Tissue / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014527:Uric Acid / Q000494:pharmacology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C587672:IL1B protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D008075:Lipoproteins, HDL; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid
keywords: Chemokines; Cytokines; Gout; Inflammation