The advanced glycation end product pentosidine correlates to IL-6 and other relevant inflammatory markers in rheumatoid arthritis.
OBJECTIVE
Oxidative stress and inflammatory processes accelerate the formation of advanced glycation end products (AGE), e.g. of pentosidine. The aim of this study was to investigate the relationships between levels of pentosidine in serum and synovial fluid, proinflammatory cytokines, other markers of inflammatory activity, and the state of radiologically visible bone destruction in patients with rheumatoid arthritis (RA).


OBJECTIVE
One hundred thirty-three nondiabetic RA patients and 56 age-matched, healthy subjects were included. Serum and synovial fluid pentosidine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor levels were determined. In 30 patients, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha and the soluble receptors sIL-2R, sIL-6R, sTNF-alpha, and RI/RII were also measured.


RESULTS
Serum levels of pentosidine were on average significantly higher in RA patients than in healthy subjects and correlated significantly to ESR, CRP, and serum levels of IL-6. Serum and synovial fluid pentosidine did not show any differences. Rheumatoid factor-positive RA patients had higher pentosidine levels in the synovial fluid than rheumatoid factor-negative patients. Correlations could not be found between pentosidine and the other cytokines or cytokine receptors measured.


CONCLUSIONS
The binding of AGE on cell receptors induces activation of nuclear factor kappa B, resulting in enhanced synthesis of proinflammatory cytokines. Moreover, AGE generation may also lead to the formation of new, immunologically relevant epitopes at synovial proteins. Both mechanisms could contribute to initiation and perpetuation of the inflammatory and destructive processes in RA.
Hein
Gert E
GE
Rheumatology and Osteology, Department of Internal Medicine III, Friedrich Schiller University of Jena, 07740 Jena, Germany. gert.hein@med.uni-jena.de
Köhler
Markus
M
Oelzner
Peter
P
Stein
Günter
G
Franke
Sybille
S
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011859:Radiography; D018121:Receptors, Cytokine / Q000097:blood; D012217:Rheumatoid Factor / Q000097:blood; D012219:Rheumatology / Q000379:methods*; D013582:Synovial Fluid / Q000737:chemistry
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D018121:Receptors, Cytokine; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D001120:Arginine; C062187:pentosidine; D008239:Lysine