Low secretion of tumor necrosis factor α, but no other Th1 or Th2 cytokines, by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis

Objective. To determine Th1 and Th2 cytokine production in patients with reactive arthritis (ReA) in relation to disease outcome and in comparison with rheumatoid arthritis (RA). Methods. Secretion of tumor necrosis factor alpha (TNF alpha), interferon-gamma, interleukin-10 (IL-10), and IL-4 by peripheral blood mononuclear cells (PBMC) from 53 patients with early ReA (disease duration <8 weeks, 64% HLA-B27 positive) and 30 patients with early, untreated RA (disease duration <6 months) was determined by enzyme-linked immunosorbent assay (ELISA) after ex vivo stimulation. Intracellular cytokine staining with quantification of positive T cells by fluorescense-activated cell sorting (FACS) was performed in 12 ReA patients and 12 Ra patients. In 27 ReA patients, cytokine secretion was measured again after 3 months, Patients were followed up for 1 year, and cytokine patterns were correlated with disease duration. Results. TNF alpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FAGS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines, ReA patients with a disease duration of greater than or equal to 6 months show,ed significantly lower TNF alpha secretion than patients,vith a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003), Furthermore, low TNF alpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNF alpha than did those who were B27 negative (338 +/- 214 pg/ml versus 512 +/- 207 pg/ml; P = 0.05), and patients with a more chronic course had a higher frequency of B27 positivity (47% versus 80%; P = 0.01). Among the 27 HLA-B27 positive patients, TNF alpha secretion in those with a disease duration of greater than or equal to 6 months was lower than that in the 7 with a disease duration of <6 months (308 +/- 167 pg/ml versus 562 +/- 308 pg/ml; P = 0.04), Conclusion. Low TNF alpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNF alpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.