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

Arthritis Rheum. 1999 Oct;42(10):2039-44. doi: 10.1002/1529-0131(199910)42:10<2039::AID-ANR3>3.0.CO;2-6.


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 (TNFalpha), 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 fluorescence-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: TNFalpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FACS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines. ReA patients with a disease duration of > or =6 months showed significantly lower TNFalpha secretion than patients with a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003). Furthermore, low TNFalpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNFalpha 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, TNFalpha secretion in those with a disease duration of > or = 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 TNFalpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNFalpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Reactive / blood
  • Arthritis, Reactive / immunology*
  • Arthritis, Reactive / physiopathology
  • Biomarkers
  • Chronic Disease
  • Cytokines / immunology
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Prohibitins
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism*


  • Biomarkers
  • Cytokines
  • PHB2 protein, human
  • Prohibitins
  • Tumor Necrosis Factor-alpha