Histamine in rheumatoid arthritis

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by a persistent inflammation of the synovium, leading to the erosion of articular cartilage and bone. Synovial mast cells and their effector molecule, histamine, receive increased attention as mediators of joint inflammation. The aim of our study was to analyse levels of free histamine in serum and joint fluid of RA patients and to evaluate the potential inflammatogenic properties of histamine in vivo and in vitro. Histamine levels were measured by an ELISA in synovial fluid and sera of RA patients and of healthy controls. Histamine levels were also assessed in plasma of RA patients undergoing anti-TNF-alpha treatment. In the murine part of the study, histamine was injected intra-articularly in the knee joint of mice and the joints were subsequently analysed with respect to induction of inflammation. RA patients displayed significantly lower levels of histamine in circulation (0.93 +/- 0.16 ng/ml) compared with the healthy controls (1.89 +/- 0.45 ng/ml, P < 0.001). Locally, in synovial fluid the levels of histamine were even lower (0.37 +/- 0.16 ng/ml, P < 0.0006). Long-term anti-TNF-alpha treatment significantly increased circulating levels of histamine in RA patients. Our experiments on animals show that histamine on its own neither induces inflammation in the joint cavity nor influences the course of HMGB1 and peptidoglycan-induced joint inflammation. Based on our experimental and clinical studies we suggest that histamine lacks harmful properties in RA.


  • M. Adlesic
  • M. Verdrengh
  • M. Bokarewa
  • Leif Dahlberg
  • S. J. Foster
  • A. Tarkowski
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)530-537
JournalScandinavian Journal of Immunology
Issue number6
Publication statusPublished - 2007
Publication categoryResearch