Objective. To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS).Patients and methods. Computed tomographyassisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in si tu hybridization.Results. Dense cellular infiltrates with varying amounts of CD3+ cells (mean f SD 53.3 f 24.1%), CD4+ cells (29.7 f 17.6%), CDS+ cells (15.8 f 11.4%), CD14+ cells (23.6 f 16.9%), CD45RO+ cells (48.4 f 23.6%), and CD45RA+ cells (4.5 f 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor a (TNFa) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor / 3 (TGFP) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique.Conclusion.

The immunohistological findings of a limited sample suggest a role for BM in sacroiliitis, for TNFalpha and IL6 in early, active lesions, and for TGFbeta1 at the time of secondary cartilage and bone proliferation.

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.

Objective. To investigate whether type 1 helper (Thl) 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-y (IFN y), tumor necrosis factor a (TNFa), interleukin-4 (IL-4), and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with Borreliu burgdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied using semiquantitative reverse transcriptasepolymerase 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 IFNy and TNFa, but little or no IL-4, upon stimulation with Bb antigen, indicating a Thl-type cytokine pattern. In SM, IFNy 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 Thl response, especially the production of

The Th1 pattern in the joint of RA patients demonstrated at the single-cell level may be important for the pathogenesis of RA and may provide a target for future immunotherapy. Our data suggest a therapeutic role for IL-4.