High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory lyme arthritis.
OBJECTIVE
To investigate the possible role of chemokines and cytokines in the pathogenesis of Lyme arthritis.


METHODS
Using cytometric bead array and flow cytometry techniques, chemokine and cytokine levels were determined in 65 synovial fluid (SF) samples and 7 synovial tissue (ST) samples from 17 patients with antibiotic-responsive Lyme arthritis and 35 patients with antibiotic-refractory Lyme arthritis seen during the past 18 years. In the ST samples, expression of chemokine receptors was measured using immunohistochemistry.


RESULTS
Before or during antibiotic therapy, when the majority of patients had positive polymerase chain reaction (PCR) results for Borrelia burgdorferi DNA, SF from patients with antibiotic-refractory arthritis contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly CXCL9 and interferon-gamma (IFNgamma). Compared with the patients whose arthritis was responsive to antibiotic treatment, those with antibiotic-refractory arthritis had significantly higher levels of CXCL9 and CXCL10 (both P<or=0.001) and CCL3, CCL4, CXCL8, IFNgamma, tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 (all P<or=0.01). During the post-antibiotic period, when the results of PCR for B burgdorferi DNA in SF and ST were uniformly negative, patients with antibiotic-refractory arthritis continued to exhibit high SF and ST levels of these chemokines and cytokines. In addition, synovial samples showed marked expression of the receptors for T cell or macrophage chemokines, CXCR3 and CCR5.


CONCLUSIONS
Patients with antibiotic-refractory Lyme arthritis have high synovial fluid levels of proinflammatory chemokines and cytokines, especially CXCL9 and IFNgamma, throughout the illness. Thus, even when antibiotic treatment reduces or completely clears the infection in these patients, the inflammatory response in synovium persists.
Shin
Junghee J
JJ
Massachusetts General Hospital, and Harvard Medical School, Boston, Massachussets 02114, USA. jjshin@partners.org
Glickstein
Lisa J
LJ
Steere
Allen C
AC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015748:Borrelia burgdorferi Group / Q000302:isolation & purification; D019743:Chemokines, CXC / Q000378:metabolism*; D002648:Child; D004269:DNA, Bacterial / Q000032:analysis; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008193:Lyme Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015846:Monokines / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D000900:Anti-Bacterial Agents; D019743:Chemokines, CXC; D004269:DNA, Bacterial; D015846:Monokines; D007371:Interferon-gamma