Crucial role of interleukin‐10/interleukin‐12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis

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Abstract
Objective. To investigate whether a predominant type 1 T helper (Thl) or Th2 cytokine pattern is present in the joints of patients with reactive arthritis (ReA), and whether the cytokine pattern can be modulated by cytokines or anticytokines. Methods. Eleven patients with ReA following infection with either Chlamydia trachomatis, Yersinia enterocolitica, or Salmonella enteritidis were investigated for the presence of Th1/Th2 cytokines in the joints. Release of the bacteria‐specific cytokines interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐10 (IL‐10), and IL‐4 was measured in synovial fluid mononuclear cells (SFMC) using enzyme‐linked immunosorbent assay and polymerase chain reaction. In the synovial membrane, secretion of IFNγ and IL‐4 was determined by immunohistologic analysis. Cytokine regulation was studied by adding cytokines and anticytokines to the cultures. Results. Upon stimulation with specific bacteria, SFMC secreted low amounts of IFNγ and TNFα, but high amounts of IL‐10. IL‐10 was responsible for the suppression of IFNγ and TNFα, as judged by the effect of adding either anti‐IL‐10 antibodies or exogenous IL‐10 to these cultures. The addition of neutralizing anti‐IL‐12 to the cultures completely abolished the effects of anti‐IL‐10, suggesting that inhibition of the Th1‐like cytokines by IL‐10 is mediated through suppression of IL‐12 synthesis. Exogenous IL‐12 clearly enhanced IFNγ and TNFα secretion. In the synovial membrane, a higher number of cells were positive for the Th2 cytokine IL‐4, compared with the amount of IFNγ‐secreting cells. Conclusion. These data indicate that a Th2 cytokine pattern predominates in the joints of patients with ReA. Since Thl cytokines are necessary for the elimination of ReA‐associated bacteria, Th2 cytokines might contribute to bacterial persistence in the joint. Therefore, the IL‐10/IL‐12 balance appears to be crucial for regulation of the cytokine pattern in the joints of patients with ReA.