Pro-inflammatory capacity of sesquiterpene lactones from asteraceae – their impact on allergic contact dermatitis

Medicinal plants of the Asteraceae family, such as Arnica montana, Tanacetum parthenium and others, are commonly used to soothe inflammatory conditions. Nonetheless these plants are known to exhibit allergenic potential after skin exposure. For both effects, sesquiterpene lactones (STLs) are held responsible. Their well known role in allergic contact dermatitis (ACD) is formation of full antigens with proteins of the skin. One of the early steps in sensitization as well as in elicitation of an ACD is the production of pro-inflammatory signals by residing keratinocytes (KC). It was an open question, whether STLs, generally considered anti-inflammatory molecules, can directly induce such signals.

The effects of selected STLs and allergy-relevant plant extracts on HaCaT KC were therefore examined in comparison to the known strong sensitizer dinitrochlorobenzene. Time-resolved mRNA microarray experiments showed that various STLs indeed induce a diverse arsenal of inflammation-associated mechanisms. Furthermore we could demonstrate that these compounds, in a concentration-dependent manner, elicit considerable changes in the levels of the pro-inflammatory cytokines IL-6, IL-8 and IFNγ in culture supernatants. Although the regulation was not consistently up- or downwards for all tested compounds, an overall increase in inflammatory mediators could be confirmed. Therefore we conclude that STLs can directly contribute to the onset of ACD by provoking keratinocytes to emit “danger signals” in form of pro-inflammatory mediators.