PMID- 10834861
OWN - NLM
STAT- MEDLINE
DCOM- 20000706
LR  - 20190503
IS  - 0003-4967 (Print)
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 59
IP  - 6
DP  - 2000 Jun
TI  - Interindividual and intra-articular variation of proinflammatory cytokines in 
      patients with rheumatoid arthritis: potential implications for treatment.
PG  - 439-47
AB  - OBJECTIVES: Assessment of the numbers and spatial distribution of cells producing 
      interleukin 1alpha (IL1alpha), interleukin 1beta (IL1beta), tumour necrosis 
      factor alpha (TNFalpha), and interleukin 6 (IL6) in the synovial membranes of 
      patients with rheumatoid arthritis (RA). METHODS: Synovial tissue specimens from 
      40 patients with RA and eight patients with non-rheumatic disease were obtained 
      by arthroscopy guided biopsy techniques or during joint surgery. A modified 
      immunohistochemical method detecting cytokine producing rather than cytokine 
      binding cells was applied to determine cytokine synthesis in fixed cryopreserved 
      sections. Computerised image analysis methods provided comparative quantitative 
      assessments. RESULTS: A wide variation between subjects was recorded for both 
      quantities and profiles of expressed cytokines, despite similar macroscopic and 
      histopathological features of inflammation. IL1alpha and IL1beta were the most 
      abundant monokines identified, though produced at different sites. IL1alpha was 
      predominantly seen in vascular endothelial cells, whereas IL1beta staining was 
      mainly shown in macrophages and fibroblasts. Concordant results for the detection 
      of TNFalpha at protein and mRNA levels were obtained with an unexpectedly low 
      number of TNFalpha producing cells compared with IL1 expressing cells in many 
      patients with RA. Specimens acquired arthroscopically from areas with maximum 
      signs of macroscopic inflammation showed an increased number of TNFalpha 
      producing cells in pannus tissue compared with that occurring in synovial villi 
      of a given joint. This clustered distribution was not found for cells expressing 
      any of the other studied cytokines. CONCLUSION: The recorded heterogeneous 
      profile of proinflammatory cytokine synthesis in the synovial membrane among 
      patients with RA may provide a clue for an understanding of the wide variation in 
      responsiveness to different modes of antirheumatic treatment between patients.
FAU - Ulfgren, A K
AU  - Ulfgren AK
AD  - Department of Medicine Unit of Rheumatology, Karolinska Hospital, Stockholm, 
      Sweden. Ann-Kristin.Ulfgren@cmm.ki.se
FAU - Grondal, L
AU  - Grondal L
FAU - Lindblad, S
AU  - Lindblad S
FAU - Khademi, M
AU  - Khademi M
FAU - Johnell, O
AU  - Johnell O
FAU - Klareskog, L
AU  - Klareskog L
FAU - Andersson, U
AU  - Andersson U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthritis, Rheumatoid/*immunology/pathology
MH  - Arthroscopy
MH  - Case-Control Studies
MH  - Cell Count
MH  - Female
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Immunohistochemistry
MH  - Interleukin-1/analysis/*biosynthesis
MH  - Interleukin-6/analysis/*biosynthesis
MH  - Male
MH  - Middle Aged
MH  - Statistics, Nonparametric
MH  - Synovial Membrane/*immunology
MH  - Tumor Necrosis Factor-alpha/analysis/*biosynthesis
PMC - PMC1753152
EDAT- 2000/06/02 09:00
MHDA- 2000/07/08 11:00
PMCR- 2003/06/01
CRDT- 2000/06/02 09:00
PHST- 2000/06/02 09:00 [pubmed]
PHST- 2000/07/08 11:00 [medline]
PHST- 2000/06/02 09:00 [entrez]
PHST- 2003/06/01 00:00 [pmc-release]
AID - 10.1136/ard.59.6.439 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2000 Jun;59(6):439-47. doi: 10.1136/ard.59.6.439.