An extract of the fern Polypodium leucotomos (Difur((R))) modulates Th1/Th2 cytokines balance in vitro and appears to exhibit anti-angiogenic activities in vivo: Pathogenic relationships and therapeutic implications

In the present study we show the capacity of an extract of the fern Polypod ium leucotomos (PLE) to partially inhibit the production of cytokines showi ng a Th1 pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated pe ripheral blood mono-nuclear cells. The percentage of inhibition was 24% for IL-2, 72% for INF-gamma and 53% for TNF-alpha. With regard to Th2 cytokine s, the addition of PLE resulted in a significant increase (33%) in IL-10 pr oduction. Surprisingly the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested. In a se cond experiment in vivo we show that, the topical application of PLE to the skin of hairless albino mice (Skh-1) significantly diminished the mast cel l infiltrate as well as the number of blood vessels triggered by chronic ul traviolet B (WB) irradiation. These data show that PLE moderately inhibits the immunological Th1 responses, thus explaining the immunosuppressive as w ell as the anti-inflammatory and antioxidant activities reported in other s tudies carried out with PLE. The clear inhibitory effect on TFN-alpha and I L-6 production strongly suggest that this may be the mechanism by which PLE : (rr) inhibits angiogenesis in vivo in the mouse model described here, and (b) prevents Langerhans' cells depletion caused by solar irradiation in hu mans. Taken together, these data suggest that PLE works through the inducti on of suppressive/anti-inflammatory cytokines such as IL-10 and/or TGF-beta which in turn appear to allow the partial deactivation of macrophages or o ther accessory cells. These features suggest that PLE could be useful in th e treatment of autoaggres-sive/inflammatory conditions due to art exacerbat ion of Th1 responses.