T cell cytokine pattern in the joints of patients with lyme arthritis and its regulation by cytokines and anticytokines

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Abstract
Objective. To investigate whether type 1 helper (Th1) or Th2 cytokines are found in the joints of patients with Lyme arthritis, and whether the cytokine pattern can be modulated by cytokines or anticytokines. Methods. The cytokine pattern in the joints of 10 patients with Lyme arthritis was investigated. Expression of interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐4 (IL‐4), and IL‐10 was measured by enzyme‐linked immunosorbent assay (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with Borrelia burgdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied using semiquantitative reverse transcriptase‐polymerase chain reaction and immunohistologic techniques. The effects of recombinant cytokines or neutralizing anticytokine antibodies on cytokine production in Bb‐stimulated SFMC were investigated by ELISA. Results. SFMC produced high amounts of IFNγ and TNFα, but little or no IL‐4, upon stimulation with Bb antigen, indicating a Th1‐type cytokine pattern. In SM, IFNγ was detectable in all patients, while the other cytokines were less frequently found. Serial sections of SM revealed that all cytokines were located in the same area. The Th1 response, especially the production of TNFα, could be down‐regulated in vitro by both endogenous and exogenous IL‐10, but not by IL‐4 or anti‐IL‐12. Conclusion. A Th1‐type cytokine pattern was found in the joints of patients with Lyme arthritis. This Th1 response could be down‐regulated by IL‐10, suggesting insufficient IL‐10 production in vivo.