CYTOKINE RELEASE OF A KERATINOCYTE MODEL AFTER INCUBATION WITH TWO DIFFERENT VISCUM ALBUM L EXTRACTS.

This study by researchers at several institutions including the International Institute for Oncological and Immunological Research and the University of California at San Francisco demonstrated that MatTek’s EpiDerm in vitro human skin tissue equivalent is an excellent in vitro model for measuring the specific pro-inflammatory cytokines released in the skin when exposed to pro-inflammatory compounds, and whether that reaction is dose dependent. When injected subcutaneously, extracts from the white berry mistletoe (Viscum album L) lead to a dose-dependent local inflammatory reaction at the injection site. From in vitro investigations with V album extracts, the release of pro-inflammatory cytokines from peripheral blood mononuclear cells and from a human skin model (Skin2 model; Advanced Tissue Sciences, La Jolla, CA) is known. This shows dose dependence for mistletoe lectin-I in the range of 0.02 ng/mL to 10.0 ng/mL. In this study, an investigation was conducted of which cytokines are released in the skin by the mistletoe lectin–standardized mistletoe extracts Viscum album QuFrF (VaQuFrF) and Iscador Qu Spzial (IQuS) (Institute Hiscia, Arlesheim, Switzerland) and whether dose dependency exists. The model used for this study is the multilayered skin model EpiDerm (MatTek Corporation, Ashland, MA), which consists of multilayered keratinocytes. The viability of the cell culture was measured after incubation with 0.01, 0.1, 0.2, 0.3, 0.5, and 15.0 ng/mL VaQuFrF or 0.01, 0.1, 0.2, 0.3, 0.5, 5.0, and 15.0 ng/mL IQuS. The release of interleukin (IL)-1á, IL-2, IL-6, IL-8, IL-10, IL-12p40+70, IL-12p70, tumor necrosis factor-á (TNF-á), interferon (IFN)-á, IFN-ã, granulocyte macrophage–colony stimulating factor, and RANTES was determined after incubation with 0.5 ng/mL of IQuS ng/mL and VaQuFrF. The dose dependency of the release of IL-1á and IL-6 after incubation with 0.5 and 15.0 ng/mL VaQuFrF or 0.5 ng/mL, 5.0 ng/mL, and 15.0 ng/mL IQuS and that of the release of IL-1á, IL-2, IL-6, IL-10, and TNF-á after incubation with 0.01 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, and 0.5 ng/mL VaQuFrF or IQuS were determined. A dose-dependent decrease of cellular viability and an increase of IL-1á, IL-6, and TNF-á as well as the release of IL-8 could be demonstrated. These results are compatible with the hypothesis that the subcutaneous injection of VaQuFrF and IQuS leads to a release of pro-inflammatory cytokines at the injection site.

Cytokines, EpiDerm, GM-CSF, Human epidermis, Inflammation, Inflammatory, Inflammatory reaction, Interleukin, Iscador, Iscador Qu Spzial (IQuS), Keratinocytes, MTS assay, Mistletoe, Normal neonatal human epidermal keratinocytes, RANTES, Skin model, TNF-a, Toxicity , Tumor necrosis factor alpha, Viability, Viscum album QUFRF (VaQuFrF)

Iscador Qu Spzial (IQuS), Viscum album QuFrF (VaQuFrF)