The Viscum album Extract Iscador P Does not Cause an Autocrine Interleukin-6 Loop in B-Non-Hodgkin’s Lymphoma Cell Lines

Abstract

Background: Single cases of clinical observations suggest the efficacy of the Viscum album (VA) extract Iscador P in the treatment of follicular B-Non-Hodgkin’s Lymphoma (B-NHL). A previously published study aroused a controversial dispute as it indicated that IL-6 serum levels are elevated following i.v. VA treatment. Increased IL-6 levels have been shown to promote the progression of B-cell neoplasia such as B-NHL. Objective of this study was to investigate whether the VA extract influences the expression of IL-6 and its receptor components in follicular B-NHL cell lines. Methods: Follicular B-NHL cell lines (WSU-NHL, DoHH-2) were incubated with clinically relevant doses of VA extract for up to 3 days. At specified time points (6, 24, 48, 72h) samples were taken and the expression of IL-6 and its receptor components were analysed by real-time-RT-PCR, flow cytometry and ELISA. Results: Treatment of follicular B-NHL cell lines with VA extract did not alter the expression level of IL-6 and its’ receptor components at any time and with any of the applied VA extract concentrations. Conclusions: Clinically relevant doses of the VA extract do not trigger an autocrine or paracrine IL-6 loop nor do they initiate IL-6 trans-signalling in follicular B-NHL cell lines.

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“…It is derived from Viscum album L., a semiparasitic plant, which is classified into three subspecies ( deciduous tree mistletoe , pine mistletoe , and fir mistletoe ) each having its particular host tree (apple tree, oak, elm, pine, and fir). Its effects are similar to those of other biological response modifiers in targeting the immune system [9–15], (review in [16]). Main components of the whole plant extract are mistletoe lectins I, II, and III and six viscotoxins and polysaccharides.…”

High levels of serum prostate‐specific antigen due to PSA producing follicular non‐Hodgkin’s lymphoma

“…IL‐6, with many previous names, including B‐cell stimulatory factor‐2 and cytotoxic T‐cell differentiation factor (CDF) (16) is a pluripotent regulatory cytokine in the immune response, inflammation and hematopoiesis. Increased IL‐6 levels have been shown to promote the progression of B‐cell non‐Hodgkin’s lymphoma (B‐NHL) (17). Furthermore, high levels of IL‐6 have been isolated from patients with NHL (18, 19).…”

Guest Editorial

“…The selection of the invited papers followed a wellfounded scientific criticism expressed by a respected oncologist, M. Hallek, Department of Internal Medicine I of the University of Cologne, Germany, in an Editorial in Onkologie [3] which accompanied an article published in the same journal [4]: "Finally, no effort was undertaken to study the actions of Iscador on cell proliferation, apoptosis or other functional parameters" [3]. This collection of papers is the scientific door-opener in the above mentioned sense, or to put it in Hallek's own words: "... more systematic functional analyses are warranted in the future to learn more about the potential stimulation of malignant cell proliferation by V. album extracts" [3].…”