Influence of anti-tumor necrosis factor therapy (Adalimumab) on regulatory T cells and dendritic cells in rheumatoid arthritis

Clin Exp Rheumatol. 2006 Jan-Feb;24(1):31-7.

Abstract

Objective: To investigate whether anti-TNF therapy could have an effect on dendritic cells (DCs) and regulatory T cells in rheumatoid arthritis (RA) patients.

Methods: A four-colour flow cytometric technique was used to measure CD4+CD25+ T cells i.e. CD4+CD25high+ (regulatory T cells) and CD4+CD25low+ (activated T cells)), DCs as well as the in vitro, intracellular, lipopolysaccharide-stimulated cytokine production of DCs.

Results: Clinical and laboratory parameters of disease activity decreased after anti-TNF treatment. Before anti-TNF therapy, RA patients demonstrated a decreased count of Th2-promoting lymphoid DCs as compared to controls and after anti-TNF therapy this decrease was sustained. Intracellular cytokine production was only found in the myeloid DCs population and there was a higher production of TNF-alpha and IL1-b as compared to healthy controls. Treatment did not alter this cytokine production. Before anti-TNF therapy, the percentage CD4+CD25+ T cells was significantly elevated in RA patients than in healthy controls.

Conclusion: These results demonstrate anti-TNF to be a potent anti-inflammatory drug, as mirrored by the decrease in clinical and biological parameters as well as the decrease in activated CD4+ T cells. However, in this study no demonstrable effect on DCs and regulatory T cells was found.

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology
  • Cell Separation
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Drug Therapy, Combination
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Severity of Illness Index
  • T-Lymphocytes, Regulatory / classification
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Adalimumab
  • Methotrexate