The allergenic potential of sesquiterpene lactones in phytomedicines from Arnica – an immunologic revision

Preparations of Arnica montana L. flowers have been used in traditional medicine since a long time to treat a variety of inflammatory diseases. The secondary metabolites that mediate the anti-inflammatory effects are sesquiterpene lactones (SLs) of the 10α-methylpseudoguaianolide type like helenalin and 11α,13-dihyrohelenalin, and their ester derivatives. Several studies have shown that SLs exert this effect in part by inhibiting activation of the transcription factor NF-κB. Despite the proven anti-inflammatory effects, Arnica preparations are often considered as strong contact sensitizers and inducers of allergic contact dermatitis. This bad reputation is based on results from a guinea pig model where different preparations from Arnica montana and their isolated SLs turned out to be strong inducers of skin erythema and on case reports in the literature. In contrast to these findings, we had no success in causing contact hypersensitivity (CHS) to the same SLs and preparations in a well accepted mouse model, on the contrary, we observed an anti-inflammatory effect of Arnica tinctures in an allergic ear swelling reaction caused by the strong contact sensitizer TNCB.

Further studies were undertaken to find out if CD4⁺CD25⁺ regulatory T cells (Treg) actively prevent CHS to Arnica tinctures. Although we failed causing CHS in CD4⁺CD25⁺ T cell-depleted mice, our preliminary studies using MHC II^0/0 mice indicate that CHS to Arnica can be induced. As in CHS to TNCB and other allergens, CD8⁺ T cells are the effector cells. Our results show that immunosuppressive mechanisms such as the action of Treg cells prevent CHS to Arnica. According to these findings, SLs and tinctures from Arnica have to be classified as weak contact sensitizers.

Acknowlegement: We gratefully acknowledge financial support from Kneipp company.