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.
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.
Authors: N Van Damme; M De Vos; D Baeten; P Demetter; H Mielants; G Verbruggen; C Cuvelier; E M Veys; F De Keyser Journal: Ann Rheum Dis Date: 2001-05 Impact factor: 19.103
Authors: J Braun; J Xiang; J Brandt; H Maetzel; H Haibel; P Wu; S Kohler; M Rudwaleit; S Siegert; A Radbruch; A Thiel; J Sieper Journal: Ann Rheum Dis Date: 2000-11 Impact factor: 19.103
Authors: S Kotake; H R Schumacher; T K Arayssi; H C Gérard; P J Branigan; A P Hudson; C H Yarboro; J H Klippel; R L Wilder Journal: Infect Immun Date: 1999-05 Impact factor: 3.441