gms | German Medical Science

Objectives: A long-lasting anti-inflammatory effect of generated catecholamine-producing tyrosine hydroxylase-positive (TH+) cells was shown in collagen type II-induced arthritis (CIA) [1]. Here, we investigated the importance of TH+ cells in another model (antigen-induced arthritis (AIA)) of rheumatoid arthritis.

Methods: TH+ cells were generated from murine bone -derived mesenchymal stem cells by specific catecholaminergic factorsa^. Antigen-induced arthritis (AIA) was induced in C57BL/6J mice and one group was treated by TH+ cell-transfer [1]. The appearance of natural TH+ cells, clinical signs of arthritis, pain and immune parameters were observed during AIA.

Results and Conclusion: In contrast to CIA, here, only a small number of natural occurring TH+ cells were detectable in spleen in the acute phase of arthritis. After TH+ cell transfer, joint swelling was only moderately reduced in acute AIA, but mice showed significantly less guarding and less reduction of withdrawal threshold for mechanical stimulation on the inflamed hind limb. These effects were attenuated towards later phases of the disease. Furthermore, in TH+ treated mice cytokines in spleen cell supernatants and in sera were not clearly altered in acute AIA. Otherwise generated TH+ cells were shown to produce significant levels of IL-4, IL-6 and TNF. Preliminary data also show a differentiation of invasive macrophages towards the M2 phenotype (Iba-1- and arginase1- positive) after TH+ transfer. The site of action of those M2-macrophages is currently under investigation.

In acute AIA, TH+ cells have rather an anti-nociceptive than an anti-inflammatory effect. This effect might be achieved by shifting invasive macrophages towards an anti-nociceptive M2 phenotype by transferred catecholaminergic cells.