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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

OBJECTIVE: To investigate whether a predominant type 1 T helper (Th1) 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-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), 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 IFN gamma 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 IFN gamma and TNF alpha, but high amounts of IL-10. IL-10 was responsible for the suppression of IFN gamma and TNF alpha, 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 IFN gamma and TNF alpha secretion. In the synovial membrane, a higher number of cells were positive for the Th2 cytokine IL-4, compared with the amount of IFN gamma-secreting cells. CONCLUSION: These data indicate that a Th2 cytokine pattern predominates in the joints of patients with ReA. Since Th1 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.[1]

References

  1. Crucial role of interleukin-10/interleukin-12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis. Yin, Z., Braun, J., Neure, L., Wu, P., Liu, L., Eggens, U., Sieper, J. Arthritis Rheum. (1997) [Pubmed]
 
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