PMID- 10211881
OWN - NLM
STAT- MEDLINE
DCOM- 19990430
LR  - 20061115
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 42
IP  - 4
DP  - 1999 Apr
TI  - Systemic viral interleukin-10 gene delivery prevents cartilage invasion by human 
      rheumatoid synovial tissue engrafted in SCID mice.
PG  - 678-85
AB  - OBJECTIVE: To assess the effects of viral interleukin-10 (vIL-10) gene delivery 
      on human rheumatoid synovial tissue. METHODS: SCID mice were engrafted 
      subcutaneously with human rheumatoid synovial tissue and homologous cartilage 
      before systemic injection of 10(9) plaque-forming units of type 5 E1a 
      Elb-deficient non-replicative adenovirus vector containing the vIL-10 gene under 
      control of the cytomegalovirus promoter (AdvIL-10; n = 10) or a control gene 
      (AdvIL-10mut; n = 7). Three weeks later, the graft was removed for histologic 
      analysis of cartilage invasion by synovial tissue. The number of CD3-positive 
      mononuclear cells was assessed in the synovial tissue by immunohistology. 
      Messenger RNA (mRNA) expression of matrix metalloproteinase 3 (MMP-3), tissue 
      inhibitor of metalloproteinases 1 (TIMP-1), and proinflammatory cytokines was 
      determined by polymerase chain reaction. RESULTS: Systemic vIL-10 gene transfer 
      resulted in high sustained production of vIL-10 protein in SCID mouse sera (mean 
      +/- SD 25 +/- 5 ng/ml on day 40 post vector injection). Moreover, vIL-10 mRNA 
      expression was detected in the synovial tissue 3 weeks after intravenous 
      injection of AdvIL-10, reflecting the gene transfer in the human graft. In 
      animals treated with AdvIL-10, cartilage invasion by rheumatoid synovial tissue 
      was significantly inhibited compared with the control vector (mean +/- SD 
      histologic score 2.5 +/- 0.52 versus 0.75 +/-0.8; P < 0.0001). The number of T 
      cells infiltrating the synovium and perichondral resorption in the animals 
      treated with AdvIL-10 gene were not significantly modified relative to the 
      control vector. In animals treated with AdvIL-10, the MMP-3-TIMP-1 balance was 
      partially restored, independent of the effect on mRNA expression of tumor 
      necrosis factor a, IL-1, IL-6, or IL-8. CONCLUSION: Systemic vIL-10 gene transfer 
      prevented cartilage invasion by synovial tissue engrafted in SCID mice. This 
      model offers the opportunity to study the biologic effects of gene transfer in 
      vivo in rheumatoid synovium.
FAU - Jorgensen, C
AU  - Jorgensen C
AD  - Service d'Immuno-Rhumatologie, Hopital Lapeyronie, and INSERM, Montpellier, 
      France.
FAU - Apparailly, F
AU  - Apparailly F
FAU - Canovas, F
AU  - Canovas F
FAU - Verwaerde, C
AU  - Verwaerde C
FAU - Auriault, C
AU  - Auriault C
FAU - Jacquet, C
AU  - Jacquet C
FAU - Sany, J
AU  - Sany J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - *Adenoviridae
MH  - Animals
MH  - Cartilage/immunology/pathology/*transplantation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/immunology
MH  - Gene Expression Regulation, Viral/immunology
MH  - *Gene Transfer Techniques
MH  - Graft Survival/immunology
MH  - Humans
MH  - Interleukin-1/genetics
MH  - Interleukin-10/blood/*genetics
MH  - Interleukin-8/genetics
MH  - Male
MH  - Matrix Metalloproteinase 3/genetics
MH  - Mice
MH  - Mice, SCID
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - Synovial Membrane/enzymology/*immunology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics
MH  - Transplantation, Heterologous
MH  - Tumor Necrosis Factor-alpha/genetics
EDAT- 1999/04/22 00:00
MHDA- 1999/04/22 00:01
CRDT- 1999/04/22 00:00
PHST- 1999/04/22 00:00 [pubmed]
PHST- 1999/04/22 00:01 [medline]
PHST- 1999/04/22 00:00 [entrez]
AID - 10.1002/1529-0131(199904)42:4<678::AID-ANR10>3.0.CO;2-S [doi]
PST - ppublish
SO  - Arthritis Rheum. 1999 Apr;42(4):678-85. doi: 
      10.1002/1529-0131(199904)42:4<678::AID-ANR10>3.0.CO;2-S.