In rheumatoid arthritis (RA) a massive loss of tyrosine hydroxylase (TH)-positive (sympathetic) nerve fibers and a clear increase of TH-positive (TH+) cells in inflamed synovial tissue of humans was found during inflammation (own previous work). TH+ cells produce catecholamines since they are equipped with all enzymes necessary for catecholamine production. In the first funding period, we demonstrated that different cells can produce catecholamines in RA: macrophages, fibroblasts, B cells, neutrophils, and mast cells. Blockade of extracellular catecholamine receptors did not influence cytokine secretion in human synoviocytes, but the increase of intracellular catecholamines induced a pronounced reduction of TNF synthesis in primary OA / RA synovial cells. Similarly, in vivo, the increase of intracellular catecholamines caused a strong anti-inflammatory effect. These results demonstrate the importance of TH+ cells in arthritis. In the next funding period, we want to examine the following aspects: 1. Role of different subpopulations of TH+ cells: do they all play the same role in inflammation? 2. Do TH+ cells play also a role in the asymptomatic phase of the disease (where are they coming from)? 3. How can TH be induced in OA / RA cells? 4. Does dopamine production of TH+ cells play a role? A better knowledge of catecholamine production can lead to the development of new therapeutic principles in arthritis.
