title: Effect of pegylated phosphatidylserine-containing liposomes in experimental chronic arthritis.
abstract: BACKGROUND
  Phosphatidylserine-containing liposomes (PSL) have been shown to reduce inflammation in experimental models of acute arthritis, by mimicking the apoptotic process. The aim of this study was to evaluate the effect of pegylated PSL (PEG-PSL) on chronic inflammation of collagen induced arthritis (CIA) in DBA/1J mice.
  
  
  METHODS
  CIA was induced in 24 DBA/1J mice (n = 6/group), which were divided into control (0.9 % saline) or treated with PEG-PSL (5, 10 and 15 mg/kg/day, subcutaneously for 20 days). Clinical score, limb histology and measurement of cytokines in knee joints of animals by ELISA and cytometric bead array (CBA) were evaluated. The in vitro study employed macrophage cultures stimulated with 100 ng/ml of LPS plus 10 ng/ml of PMA and treated with 100 μM PEG-PSL.
  
  
  RESULTS
  Resolution of the disease in vivo and the inflammatory process in vitro were not observed. PEG-PSL, in doses of 10 and 15 mg/kg, were not shown to reduce the score of the disease in animals, whereas with the dose of 5 mg/kg, the animals did not show the advanced stage of the disease when compared to the controls. The PEG- PSL 5, 10 and 15 mg/kg treatment groups did not show significant reduction of TNF-α, IL-1β, IL-6, IL-2 and IFN-γ when compared to the controls. Disease incidence and animal weights were not affected by treatment. Regarding the paw histology, PEG-PSL did not yield any reductions in the infiltrating mononuclear, synovial hyperplasia, extension of pannus formation, synovial fibrosis, erosion of cartilage, bone erosion or cartilage degradation. The concentration of 100 μM of PEG-PSL has not been shown to reduce inflammation induced by LPS/PMA in the in vitro study. Treated groups did not show any reduction in inflammatory cytokines in the knee joints of animals affected by the disease compared to the control, although there were higher concentrations of TGF-β1 in all experimental groups.
  
  
  CONCLUSIONS
  The experimental model showed an expression of severe arthritis after the booster. TGF-β1 as well other pro inflammatory cytokines were presented in high concentrations in all groups. PEG-PSL had no impact on the clinical score, the histopathology from tibial-tarsal joints or the production of cytokines in the knee joints. Other alternatives such as dosage, route of administration, and as an adjunct to a drug already on the market, should be evaluated to support the use of PEG-PSL as a new therapeutic tool in inflammatory diseases.
authors.affiliation: Biotechnology and Bioprocess Engineering, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. pc_ibc@yahoo.com.br.
authors.forename: Paulo Cm
authors.initials: PC
authors.lastname: Urbano
authors.affiliation: Biotechnology and Bioprocess Engineering, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. vanetesoccol@gmail.com.
authors.forename: Vanete T
authors.initials: VT
authors.lastname: Soccol
authors.affiliation: Rheumatology Department, Hospital de Clínicas de Porto Alegre (HCPA), Rio Grande do Sul, Brazil. viviont@gmail.com.
authors.forename: Vivian N
authors.initials: VN
authors.lastname: Teixeira
authors.affiliation: Rheumatology Department, Hospital de Clínicas de Porto Alegre (HCPA), Rio Grande do Sul, Brazil. patty.go@gmail.com.
authors.forename: Patrícia G
authors.initials: PG
authors.lastname: Oliveira
authors.affiliation: Rheumatology Department, Hospital de Clínicas de Porto Alegre (HCPA), Rio Grande do Sul, Brazil. lidifilippin@gmail.com.
authors.forename: Lidiane I
authors.initials: LI
authors.lastname: Filippin
authors.affiliation: Statistical Laboratory (LABEST), Universidade Federal do Paraná (UFPR), Curitiba, Paraná, Brazil. wbonat@gmail.com.
authors.forename: Wagner H
authors.initials: WH
authors.lastname: Bonat
authors.affiliation: Department of Cell Biology, Research Laboratory of Inflammatory Cells and Neoplastic, Universidade Federal do Paraná (UFPR), Curitiba, Paraná, Brazil. krokoli@hotmail.com.
authors.forename: Carolina
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Department of Cell Biology, Research Laboratory of Inflammatory Cells and Neoplastic, Universidade Federal do Paraná (UFPR), Curitiba, Paraná, Brazil. gustavo.r.rossi@hotmail.com.
authors.forename: Gustavo R
authors.initials: GR
authors.lastname: Rossi
authors.affiliation: Rheumatology Department, Hospital de Clínicas de Porto Alegre (HCPA), Rio Grande do Sul, Brazil. rxavier10@gmail.com.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Xavier
authors.affiliation: Rheumatology Service and Internal Medicine, Hospital de Clínicas de Curitiba, Universidade Federal do Paraná (UFPR), Rua Alvaro Alvin, 224 casa 18, Curitiba, Paraná, 80440080, Brazil. Valderilio@hotmail.com.
authors.forename: Valderilio F
authors.initials: VF
authors.lastname: Azevedo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018836:Inflammation Mediators / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008811:Mice, Inbred DBA; D010718:Phosphatidylserines / Q000008:administration & dosage / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008081:Liposomes; D010718:Phosphatidylserines; D053773:Transforming Growth Factor beta1; D011092:Polyethylene Glycols; D013755:Tetradecanoylphorbol Acetate