Differences in synovial fluid levels of matrix metalloproteinases suggest separate mechanisms of pathogenesis in Lyme arthritis before and after antibiotic treatment.
The cause of persistent arthritis in patients with Lyme disease who have received standard antibiotic therapy remains an area of debate. In this study, synovial fluid levels of matrix metalloproteinases (MMPs) were compared in persons with untreated and antibiotic-resistant Lyme arthritis. Levels of MMP-1 and MMP-3, as determined by ELISA, were higher in untreated patients (P=.0064 and P=.002, respectively), whereas levels of MMP-8 and MMP-9 were higher in antibiotic-resistant patients (P=.0002 and P=.0014, respectively). In vitro studies of chondrocyte cultures infected with Borrelia burgdorferi revealed induction of MMP-1 and MMP-3 but not of MMP-8 or MMP-9. Neither Staphylococcus aureus nor lipopolysaccharide stimulated MMP-1 or MMP-3 release from these cells. The mechanism of recognition of B. burgdorferi may be through CD14 and toll-like receptor-2, which were up-regulated in the presence of B. burgdorferi. These findings suggest different stimuli for MMP induction in untreated and antibiotic-resistant Lyme arthritis.
Lin
B
B
New England Medical Center, Tufts University School of Medicine, Tupper Research Institute, Department of Medicine, Boston, Massachusetts 02111, USA.
Kidder
J M
JM
Noring
R
R
Steere
A C
AC
Klempner
M S
MS
Hu
L T
LT
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015748:Borrelia burgdorferi Group / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000201:enzymology / Q000382:microbiology; D004352:Drug Resistance, Microbial; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008193:Lyme Disease / Q000188:drug therapy* / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology / Q000201:enzymology / Q000382:microbiology
D000900:Anti-Bacterial Agents; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1